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1.
Rev. cuba. hematol. inmunol. hemoter ; 37(1): e1310, ene.-mar. 2021.
Article in Spanish | LILACS, CUMED | ID: biblio-1251720

ABSTRACT

Introducción: Los síndromes mielodisplásicos constituyen un grupo heterogéneo de desórdenes hematológicos clonales adquiridos, que afectan la célula madre. Se caracterizan morfológicamente por: hematopoyesis ineficaz, citopenias periféricas progresivas, displasia en uno o más linajes celulares y tendencia evolutiva a leucemia aguda. Los avances recientes en la comprensión de los mecanismos genéticos y moleculares de los síndromes mielodisplásicos, han revelado la asociación entre alteraciones inmunológicas y las mutaciones recurrentes. Las células de la respuesta inmune innata y adaptativa, así como diversos mediadores solubles liberados por ellas, pueden establecer una respuesta antitumoral protectora o, por el contrario, inducir eventos de inflamación crónica que favorezcan la promoción y progresión de esta enfermedad. Objetivos: Resumir los conocimientos actuales de la relación sistema inmune-síndromes mielodisplásicos, enfatizando en las células inmunes del microambiente de la médula ósea y su importancia en la clínica de la enfermedad. Métodos: Se realizó investigación bibliográfica-documental acerca del tema. Se consultaron las bases de datos Scielo y Pubmed. Conclusiones: La comprensión de la función dual que ejerce el sistema inmune en los síndromes mielodisplásicos, constituye un desafío y son necesarios estudios clínicos rigurosos para poder establecer el valor de la manipulación del sistema inmune como una forma posible de tratamiento de esta enfermedad(AU)


Introduction: Myelodysplastic syndromes (MDS) constitute a heterogeneous group of acquired clonal hematological disorders that affect the stem cell. These are characterized morphologically and clinically by: ineffective hematopoiesis, progressive peripheral cytopenia, dysplasia in one or more cell lineages, in most of cases and evolutionary tendency to acute leukemia. Recent advances in understanding the genetic and molecular mechanisms of MDS have revealed the association between immunological alterations and recurrent mutations. Cells of the innate and adaptive immune response, as well as various soluble mediators released by them, can establish a protective antitumor response or, on the contrary, induce events of chronic inflammation that favor the promotion and progression of this disease. Objective: To summarize the current knowledge of the immune system-MDS relationship, emphasizing the immune cells of the bone marrow microenvironment and their importance in the clinic of the disease. Methods: A bibliographic-documentary research was carried out on the subject. The Scielo and Pubmed databases were consulted. Conclusions: Understanding the dual role of the immune system in MDS constitutes a challenge and rigorous clinical studies are necessary to establish the value of manipulating the immune system as a possible form of treatment of this disease(AU)


Subject(s)
Humans , Stem Cells , Myelodysplastic Syndromes/complications , Leukemia , Adaptive Immunity , Hematopoiesis/genetics , Immune System/physiopathology , Inflammation/diagnosis
2.
Journal of Experimental Hematology ; (6): 1690-1694, 2021.
Article in Chinese | WPRIM | ID: wpr-922319

ABSTRACT

Hematopoietic stem cells (HSCs) reside at the top of the hierarchy and have the ability to differentiate to variety of hematopoietic progenitor cells (HPCs) or mature hematopoietic cells in each system. At present, the procress of HSC and HPC differentiating to the complete hematopoietic system under physiological and stressed conditions is poorly understood. In vivo lineage tracing is a powerful technique that can mark the individual cells and identify the differentiation pathways of their daughter cells, it takes as a strong technical system to research HSC. Traditional lineage tracing studies mainly rely on imaging techniques with fluorescent dyes and nucleic acid analogs. Recently, newly cell tracing technologies have been invented, and the combination of clonal tracing and DNAsequencing technologies have provided a new perspective on cell state, cell fate, and lineage commitment at the single cell level. In this review, these new tracing methods were introduce and discuss, and their advantages over traditional methods in the study of hematopoiesis were summarized briefly.


Subject(s)
Cell Differentiation , Hematopoiesis , Hematopoietic Stem Cells
3.
Journal of Experimental Hematology ; (6): 1972-1976, 2021.
Article in Chinese | WPRIM | ID: wpr-922234

ABSTRACT

There are more than 150 types of chemical modifications in RNA, mainly methylation, which are widely distributed in all kinds of RNA, including messenger RNA, transfer RNA, ribosomal RNA, non-coding small RNA and long non-coding RNA. In recent years, the identification of RNA methylation modification enzymes and the development of high-throughput sequencing technology at transcriptome level laid a foundation for revealing the expression and function of genes regulated by chemical modification of RNA. In this review, the most recent advances of RNA methylation, especially N6-methyladenosine (m


Subject(s)
Adenosine/metabolism , Hematopoiesis , Humans , Methylation , RNA/metabolism
4.
Article in Chinese | WPRIM | ID: wpr-880170

ABSTRACT

OBJECTIVE@#To analyze the dynamic molecular expression characteristics of single cell RNA binding proteins (RBPs) in the development of mouse embryonic hematopoitic stem cells (HSCs), and obtain the functional research target RNA splicing factor--Mbnl1, to clarify the function of Mbnl1 involved in regulating mouse embryonic HSC development.@*METHODS@#Bioinformatics was used to analyze the single-cell transcriptome data of mouse embryos during HSC development, and the single-cell RBP dynamic molecular expression maps in HSC development was obtained. Mbnl1 was obtained by combining differential analysis and literature research screening. The Mbnl1-knockout mouse model was constructed by the CRISPER/Cas9 technology. Aorta-gonad-mesonephros (AGM) and yolk sac (YS) tissue in two genotype embryos of Mbnl1@*RESULTS@#The in vitro CFU-C experiment of hematopoietic cells preliminarily indicated that there was no significant difference in the number of cell colonies in AGM region and YS transformed by the two genotypes of Mbnl1@*CONCLUSION@#Through functional experiments in vivo and in vitro, it has been confirmed that knockout of the RNA splicing factor--Mbnl1 does not affect the development of HSPC in AGM region of mouse embryo.


Subject(s)
Animals , DNA-Binding Proteins , Gonads , Hematopoiesis , Hematopoietic Stem Cells , Mesonephros , Mice , RNA-Binding Proteins/genetics , Yolk Sac
5.
Rev. cuba. hematol. inmunol. hemoter ; 36(3): e1201, jul.-set. 2020. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1156439

ABSTRACT

Introducción: La anemia sideroblástica es un trastorno hematológico que altera el proceso de la hematopoyesis, en la cual se ve afectada en mayor proporción la línea eritroide. Además, se presentan alteraciones en la síntesis del grupo hemo por disfunción mitocondrial en las células de la médula ósea. Objetivo: Indagar sobre la anemia sideroblástica, sus variables y los diferentes tipos de presentación que puede tener esta enfermedad. Métodos: Se llevó a cabo una revisión de la literatura en las bases de datos MEDLINE, EMBASE, Lilacs y ScienceDirect, con los descriptores: anemia sideroblástica, hematopoyesis, anomalías congénitas y 5-aminolevulinato sintetasa, en español e inglés. Se seleccionaron 26 artículos relacionados. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Es una enfermedad de origen congénito o secundario a otros procesos como el consumo de alcohol o inducido por algunos medicamentos. Se presenta con poca frecuencia y, en su mayoría, el diagnóstico se hace mediante estudios de laboratorio, como extendido de sangre periférica, estudio de médula ósea, a los que se les pueden aplicar diversas tinciones, realizar secuenciación o incluso realizar reacción en cadena de polimerasa. Conclusión: La anemia sideroblástica es una enfermedad puede relacionarse con otras alteraciones hematológicas que modifican el metabolismo del hierro. El tratamiento curativo es la trasfusión de hemocomponentes y debe hacerse un enfoque individualizado de cada paciente según el tipo de anemia sideroblástica(AU)


Introduction: Sideroblastic anemia is a hematological disorder that alters the hematopoiesis process. This condition affects, to a great extent, the erythroid line. In addition, alterations occur in the synthesis of the heme group due to mitochondrial dysfunction in the bone marrow cells. Objective: To investigate sideroblastic anemia, its variables and the different types of presentation of this disease. Methods: A literature review was carried out in the MEDLINE, EMBASE, Lilacs and ScienceDirect databases, using the descriptors anemia sideroblástica [sideroblastic anemia], hematopoyesis [hematopoiesis], anomalías congénitas [congenital anomalies] and 5-aminolevulinato sintetasa [5-aminolevulinate synthetase], in Spanish and English. Twety-six articles related to the topic were selected. An analysis and summary of the revised bibliography was carried out. Information analysis and synthesis: It is a disease of congenital origin or secondary to other processes such as alcohol consumption or induced by some medications. It occurs infrequently and its diagnosis is mostly made through laboratory studies, such as peripheral blood smear and bone marrow study, to which various stains can be applied, as well as sequencing or even polymerase chain reaction. Conclusion: Sideroblastic anemia is a disease that can be related to other hematological alterations that modify iron metabolism. The curative treatment is the transfusion of blood components. An individualized approach should be used according to the type of sideroblastic anemia(AU)


Subject(s)
Humans , Hematopoiesis/physiology , Anemia, Sideroblastic/genetics , Anemia, Sideroblastic/therapy
6.
Journal of Experimental Hematology ; (6): 1044-1048, 2020.
Article in Chinese | WPRIM | ID: wpr-827164

ABSTRACT

Abstract  Hematopoietic stem cells are able to self-renewal and differentiate to all blood lineages. With the development of new technologies, recent studies have proposed the revised versions of hematopoiesis. In the classical model of hematopoietic differentiation, HSCs were located at the apex of hematopoietic hierarchy. During differentiation process, HSCs progressively lose self-renewal potential to be commited to progenitors with restricted differentiation potential. For instance, HSCs first give rise to multipotent progenitor cells, then produce bipotent and unipotent progenitors, and finally differentiate to mature blood cells. For the differentiation of megakaryocytes, common myeloid progenitors derived from HSCs give rise to megakaryocyte-erythrocyte progenitors and then develop to megakaryocytes. However, recent results show that megakaryocytes can be directly generated from HSCs without multipotent or bipotent phases. Alternatively, platelet-biased HSCs produce megakaryocyte progenitors. In this article, recent advances in the hematopoiesis and megakaryocyte differentiation pathway are reviewed.


Subject(s)
Cell Differentiation , Cell Lineage , Hematopoiesis , Hematopoietic Stem Cells , Megakaryocytes , Multipotent Stem Cells
7.
Journal of Experimental Hematology ; (6): 1349-1356, 2020.
Article in Chinese | WPRIM | ID: wpr-827113

ABSTRACT

OBJECTIVE@#To investigate the effect of PDGFRα stromal cells derived SCF on hematopoiesis of adult mice.@*METHODS@#Pdgfrα-CreER; R26-tdTomato mice model was constructed, and the proportion and distribution of PDGFRα cells in the liver, spleen, lung, kidney and bone marrow were analyzed by flow cytometry and confocal microscopy. Then the Pdgfrα-CreER; Scf mice model was further constructed, the Scf in PDGFRα was knocked out specifically, the effect of Scf-knocked out in PDGFRα stromal cells in the propitiation of HSPCs in the bone marrow was analyzed by flow cytometry. The effect of SCF on the proportion on number of peripheral blood cells in mice was analyzed by whole blood analyzer.@*RESULTS@#After Scf was knocked out in PDGFRα stromal cells, the propitiation and number of LKS- cell, LKS+ cell, HSC, MPP1, MKP, PreGM, PreMegE, and CFU-E in the bone marrow of mice was decreased, as well as in the number of red blood cells and hemoglobin concentration of peripheral blood. However, Scf knocked out from PDGFRα cells showed no effect on the hematopoiesis in spleen.@*CONCLUSION@#specific knocked out of Scf in PDGFRα stromal cells in adult mice can decrease the proportion of HSPCs in the bone marrow and the number of red blood cells in peripheral blood, and finally lead to anemia in mice.


Subject(s)
Animals , Bone Marrow , Bone Marrow Cells , Hematopoiesis , Mice , Receptor, Platelet-Derived Growth Factor alpha , Stem Cell Factor
9.
Braz. j. med. biol. res ; 52(6): e8424, 2019. tab, graf
Article in English | LILACS | ID: biblio-1001535

ABSTRACT

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.


Subject(s)
Animals , Rabbits , Leukemia, Myeloid, Acute/genetics , CCAAT-Enhancer-Binding Protein-alpha/genetics , Haploinsufficiency/genetics , Hematopoiesis/genetics , Phenotype , Transcription Factors/genetics , Translocation, Genetic/genetics , Mice, Transgenic , Acute Disease , Flow Cytometry , Genotype
10.
S. Afr. med. j. (Online) ; 109(8): 41-46, 2019. ilus
Article in English | AIM, AIM | ID: biblio-1271228

ABSTRACT

Human immunodeficiency virus (HIV) infection not only leads to a compromised immune system, but also disrupts normal haematopoiesis, resulting in the frequent manifestation of cytopenias (anaemia, thrombocytopenia and neutropenia). Although there is a definite association between the severity of cytopenia and HIV disease stage, this relationship is not always linear. For example, cytopenias such as thrombocytopenia may occur during early stages of infection. The aetiology of these haematological abnormalities is complex and multifactorial, including drug-induced impaired haematopoiesis, bone marrow suppression due to infiltration of infectious agents or malignant cells, HIV-induced impaired haematopoiesis, and several other factors. In this review, we describe the frequencies of anaemia, thrombocytopenia and neutropenia reported for HIV-infected, treatment-naïve cohorts studied in eastern and southern sub-Saharan African countries. We present a rational approach for the use of diagnostic tests during the workup of HIV-infected patients presenting with cytopenia, and discuss how HIV impacts on haematopoietic stem/progenitor cells (HSPCs) resulting in impaired haematopoiesis. Finally, we describe the direct and indirect effects of HIV on HSPCs which result in defective haematopoiesis leading to cytopenias


Subject(s)
HIV Serosorting , Hematopoiesis
11.
São Paulo; s.n; s.n; 2019. 148 p. graf, tab.
Thesis in English | LILACS | ID: biblio-996797

ABSTRACT

Protein malnutrition (PM) causes anemia and leukopenia by reduction of hematopoietic precursors and impaired production of mediators that induce hematopoiesis, as well as structural and ultrastructural changes in the bone marrow (BM) extracellular matrix. Hematopoiesis occurs in the bone marrow (BM) in distinct regions called niches, which modulate the processes of differentiation, proliferation and self-renewal of the hematopoietic stem cell (HSC). The perivascular niche, composed mainly by mesenchymal stem cells (MSC) and endothelial cells (EC), is the major modulator of HSC and its function extends to the migration of mature hematopoietic cells into the peripheral blood through the production of cytokines and growth factors. Thus, our hypothesis is that PM changes the perivascular niche and our objective is to evaluate whether PM affects the modulatory capacity of MSC and EC on hematopoiesis. C57BL/6 male mice were divided into Control and Malnourished groups, which received for 5 weeks, respectively, a normal protein diet (12% casein) and a low protein diet (2% casein). After this period, animals were euthanized, nutritional and hematological evaluations were performed, featuring the PM. We performed leukemic myelo-monoblasts cells transplantation and observed that these cells have a lower proliferation rate and are rather in the cell cycle G0/G1 phases in malnourished mice, indicating that the BM microenvironment is compromised in PM. MSC were isolated, characterized and differentiated in vitro into EC cells, which were evidenced by CD31 and CD144 markers. We performed the quantification of HSC and hematopoietic progenitors, as well as some regulators of proliferation and differentiation, ex vivo and after cultures with MSC or EC. We observed that PM reduces HSC and hematopoietic progenitors ex vivo. In PM, MSC promote increase in HSC and suppress hematopoietic differentiation, whereas ECs induce cell cycle arrest. Additionally, we verified that PM affects granulopoesis by decreasing the expression of G-CSFr in granule-monocytic progenitors. Thus, we conclude that PD compromises hematopoiesis due to intrinsic alterations in HSC, as well as alterations in the medullary perivascular niche


A desnutrição proteica (DP) provoca anemia e leucopenia decorrente da redução de precursores hematopoéticos e comprometimento da produção de mediadores indutores da hematopoese. A hematopoese ocorre na medula óssea (MO) em regiões distintas chamadas de nichos, que modulam os processos de diferenciação, proliferação e auto renovação da célula tronco hematopoiética (CTH). O microambiente perivascular, composto principalmente por células tronco mesenquimais (CTM) e células endoteliais (CE), é o principal modulador das CTH e sua função se estende até a migração das células hematopoiéticas maduras para o sangue periférico, através da produção de citocinas e fatores de crescimento. Dessa forma, nossa hipótese é que a DP altera o microambiente perivascular e objetivamos avaliar se a DP afeta a capacidade modulatória das CTM e CE sobre a hematopoese. Utilizamos camundongos C57BL/6 machos, divididos em grupos Controle e Desnutrido, sendo que o grupo Controle recebeu ração normoproteica (12% caseína) e o grupo Desnutrido recebeu ração hipoproteica (2% caseína), ambos durante 5 semanas. Após este período, os animais foram eutanasiados, foi realizada a avaliação nutricional e hematológica, caracterizando a DP. Realizamos transplantes de mielomonoblastos leucêmicos e observamos que estas células apresentam menor taxa de proliferação e se encontram em maior quantidade nas fases G0/G1 do ciclo celular em camundongos desnutridos, indicando que o microambiente medular está comprometido. Isolamos CTM, que foram caracterizadas e diferenciadas in vitro em CE, o que foi evidenciado pelos marcadores CD31 e CD144. Quantificamos CTH e progenitores hematopoéticos, bem como reguladores de proliferação e diferenciação, ex vivo e após culturas com CTM ou CE. Observamos que a DP reduz CTH e progenitores hematopoéticos ex vivo. Na DP, as CTM promovem incremento de CTH e suprimem a diferenciação hematopoética, enquanto que as CE induzem parada no ciclo celular. Adicionalmente, observamos que a DP afeta a granulopoese por diminuição da expressão de G-CSFr nos progenitores grânulo-monocíticos. Dessa forma, concluímos que a DP compromete a hematopoese por alterações intrínsecas na CTH, como também por alterações ocasionadas no microambiente perivascular medular


Subject(s)
Animals , Male , Mice , Protein Deficiency/complications , Hematopoiesis , Endothelial Cells/classification , Tumor Microenvironment
12.
Journal of Experimental Hematology ; (6): 1711-1716, 2019.
Article in Chinese | WPRIM | ID: wpr-781408

ABSTRACT

Abstract  The physiological hematopoiesis depends on the programmed expression of a series of gene regulated by mechanisms at various levels. Currently, the epigenetic regulation has been considered as the most important mechanism during hematopoietic differentiation, resulting in a specific epigenomic landscape in the hematopoietic stem/progenitor cells. We try to concisely review the epigenetic mechanisms, including the genomic methylation, the histone modifications and the expression profiles of noncoding RNA, illustrating briefly the differentiation from the hematopoietic stem/progenitor cells to to the erythroid, myeloid and lymphoid cells.


Subject(s)
Cell Differentiation , Epigenesis, Genetic , Epigenomics , Hematopoiesis , Hematopoietic Stem Cells
13.
Article in English | WPRIM | ID: wpr-777599

ABSTRACT

BACKGROUND@#We reported that human T cell leukemia virus 1 (HTLV-1) infection is positively associated with atherosclerosis. Recent evidence has revealed a close association of periodontitis with atherosclerosis, endothelial dysfunction, and disruption of the microcirculation. However, the association between HTLV-1 and advanced periodontitis has not been investigated to date. Since hematopoietic activity is closely linked to endothelial maintenance activity and is known to decline with age, we hypothesized that the state of hematopoietic activity influenced the association between HTLV-1 and advanced periodontitis in elderly participants.@*METHODS@#A cross-sectional study was performed including 822 elderly participants aged 60-99 years who participated in a dental health check-up. Advanced periodontitis was defined as a periodontal pocket ≥ 6.0 mm. Participants were classified as having low or high hematopoietic activity according to the median values of reticulocytes.@*RESULTS@#HTLV-1 infection was positively related to advanced periodontitis among participants with lower hematopoietic activity (lower reticulocyte count), but not among participants with higher hematopoietic activity (higher reticulocyte count). The adjusted odds ratio (95% confidence interval) considering potential confounding factors was 1.92 (1.05-3.49) for participants with a lower reticulocyte count and 0.69 (0.35-1.36) for participants with a higher reticulocyte count.@*CONCLUSIONS@#Among elderly participants, the association between HTLV-1 infection and advanced periodontitis is influenced by hematopoietic activity. Since hematopoietic activity is associated with endothelial maintenance, these findings provide an efficient tool for clarifying the underlying mechanism of the progression of periodontitis among elderly participants.


Subject(s)
Aged , Aged, 80 and over , Cross-Sectional Studies , Female , HTLV-I Infections , Hematopoiesis , Physiology , Human T-lymphotropic virus 1 , Physiology , Humans , Japan , Epidemiology , Male , Middle Aged , Odds Ratio , Periodontitis , Epidemiology , Virology , Prevalence , Risk Factors
14.
Article in English | WPRIM | ID: wpr-762445

ABSTRACT

The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.


Subject(s)
Diagnosis , Diagnosis, Differential , Gene Frequency , Hematologic Neoplasms , Hematopoiesis , Humans , Mortality
15.
Article in English | WPRIM | ID: wpr-764060

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet well understood. METHODS: BM cells were harvested from femurs of mice and analyzed using flow cytometry. Human PVCs were cultured in serum-free α-MEM. After 24hrs, PVC-CM was collected and filtered through a 0.22 μm filter. RESULTS: In this study, we showed that hyperglycemia alters hematopoietic composition in the BM, which can partially be restored via paracrine mechanisms, including perivascular cells (PVCs) and NADPH oxidase (NOX) inhibition in mice with streptozotocin-induced diabetes. Prolonged hyperglycemic conditions resulted in an increase in the frequency and number of long-term hematopoietic stem cells as well as the number of total BM cells. The altered hematopoiesis in the BM was partially recovered by treatment with PVC-derived conditioned medium (CM). Long-term diabetes also increased the number of myeloid-derived suppressor cells in the BM, which was partially restored by the administration of PVC-CM and diphenyleneiodonium (DPI), a NOX inhibitor. We further showed the downregulation of ERK and p38 phosphorylation in BM cells of diabetic mice treated with PVC-CM and DPI. This may be associated with dysfunction of hematopoietic cells and promotion of subsequent diabetic complications. CONCLUSIONS: Our data suggested that alterations in BM hematopoietic composition due to prolonged hyperglycemic conditions might be restored by improvement of the hematopoietic microenvironment and modulation of NOX activity.


Subject(s)
Animals , Bone Marrow , Culture Media, Conditioned , Diabetes Complications , Down-Regulation , Femur , Flow Cytometry , Hematopoiesis , Hematopoietic Stem Cells , Humans , Hyperglycemia , Mice , NADP , NADPH Oxidases , Phosphorylation
16.
Article in English | WPRIM | ID: wpr-759594

ABSTRACT

BACKGROUND: Cord blood (CB) is a reliable source of hematopoietic stem cells, and its utilization in stem cell transplantation is increasing continuously. The CD34+ cell count is arguably one of the most important parameters for evaluating the quality of a cord blood unit (CBU), but there is little evidence on the post-genetic modifications that can affect the CD34+ cell counts. In this study, the difference in the miRNA expression profiles between low and high CD34+ CBU was evaluated. METHODS: Paired CB and maternal samples with low (0.9%) were selected for analysis. MicroRNA profiling was performed, and differentially expressed miRNA were identified. In addition, gene ontology analysis was conducted on the miRNA to elucidate the genes that could potentially affect the CD34+ cell count. RESULTS: Ten miRNA were identified to show significantly different expression between the low and high CD34+ groups. Four of the 10 miRNA were hematopoiesis-related (miR-199a-5p, miR-22-5p, miR-140-5p, and miR-181b-5p). From a total of 119 associated genes, nine (CALCA, FARP2, FSHR, ITGAM, MELK, MLF1, PRG4, TREM2 and VCAM1) were associated with two or more of the aforementioned miRNA. CONCLUSION: This is the first study that examined the difference in the miRNA expression profiles between high and low CD34+ CB cells and revealed the relevant genes associated with hematopoiesis. These results provide basic insight into the genetic processes involving hematopoietic stem cell proliferation.


Subject(s)
Cell Count , Fetal Blood , Gene Ontology , Genetic Phenomena , Hematopoiesis , Hematopoietic Stem Cells , MicroRNAs , Stem Cell Transplantation , Stem Cells
17.
Immune Network ; : e12-2019.
Article in English | WPRIM | ID: wpr-740216

ABSTRACT

Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_Atg5(−/−) mice. The proliferation of Lin⁻Sca-1⁺c-Kit⁺ HSCs was aberrant in bone marrow of Vav_Atg5(−/−) mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.


Subject(s)
Anemia , Animals , Autophagy , Bone Marrow , Erythrocytes , Hematopoiesis , Hematopoietic Stem Cells , Hematopoietic System , Homeostasis , Lymphopenia , Mice , Mitochondria , Stem Cells
18.
Article in English | WPRIM | ID: wpr-741643

ABSTRACT

Hematopoiesis has a pivotal role in the maintenance of body homeostasis. Ironically, several hematological disorder caused by chemicals, drugs, and other environmental factors lead to severe bone marrow failure. Current treatments like stem cell transplantation and immunosuppression remain ineffective to ameliorate this diseases. Therefore, a newtreatment to overcome this entity is necessary, one of them by promoting the usage of medicinal plants. Thus, this study aimed to evaluate the hematopoiesis potency of S. javanica berries and leaves extracts in chloramphenicol (CMP)-induced aplastic anemia mice model. In this present study, several types of blood progenitor cell such as TER-119⁺VLA-4⁺ erythrocytes lineage, Gr-1⁺ granulocytes, and B220⁺ B-cell progenitor cells were evaluated by flow cytometry analysis. Accordingly, we revealed that S. javanica berries and leaves extracts significantly promoted TER-119⁺VLA-4⁺ erythrocytes lineage and Gr-1⁺ granulocytes after exposed by CMP. Thus, these results suggested that S. javanica berries and leaves extracts might have hematopoiesis activity in CMP-induced aplastic anemia mice model.


Subject(s)
Anemia, Aplastic , Animals , B-Lymphocytes , Bone Marrow , Chloramphenicol , Erythrocytes , Flow Cytometry , Fruit , Granulocytes , Hematopoiesis , Homeostasis , Immunosuppression , Iron , Mice , Plants, Medicinal , Sambucus , Stem Cell Transplantation , Stem Cells
19.
Article in English | WPRIM | ID: wpr-776623

ABSTRACT

Although the foundations and evolution of Chinese medicine and Western medicine are very different, an increasing amount of research has revealed that those Eastern medicine principles practiced over thousands of years are confirmed by new technologies applied to the basic science of the human body. Recent scientific discoveries present enticing opportunities to reconcile Chinese medicine theories with Western biomedicine. Is there a trend toward the convergence of Eastern and Western medicine? Four studies which exemplify the potential for convergence are described in this article. The studies present findings in regard to mesentery, interstitium, a gut-lung axis, and lung-centered hematopoiesis, and were published recently in leading journals such as Science, Nature, and Lancet.


Subject(s)
Hematopoiesis , Humans , Medicine, Chinese Traditional , Meridians , Organ Specificity
20.
Article in Chinese | WPRIM | ID: wpr-771913

ABSTRACT

OBJECTIVE@#To investigate the effect of Rictor on the hematopoiesis of fetal liver by specific knock-out of Rictor in hematopoietic cells of Vav-Cre mice.@*METHODS@#E12.5 0.08ee fetal liver cells from the experimental group Vav-Cre; Rictor embryos and control group Rictor or Rictor embryos were transplanted to recipients respectively to observe the effect of Rictor on reconstitution ability of hematopoietic stem cells. In the meantime, E14.5 0, 10, 20, 40, 60, 80 sorted hematopoietic stem cells from the Vav-Cre; Rictor fetal liver of experimental group and Rictor or Rictor fetal liver of control group were transplanted in to recipients to analyze the numbers of functional hematopoietic stem cells after Rictor was knocked-out. Furthermore, the self-renewal capacity was investigated by secondary transplantation of BM cells from primary recipients that had been successfully repopulated with E12.5 fetal liver-derived cells and by cell cycle analysis.@*RESULTS@#All the recipients receiving E12.5 Rictor or Rictor cells were repopulated (8/8, from 2 independent experiments) with an average chimerism of 77.2%±11.1% at 4 months post-transplantation, which resulted in 57 LT-RU per FL. In comparison, 8 out of 8 recipients receiving Vav-Cre; Rictor cells were repopulated with significantly reduced chimerism (37.0%±16.3%) (P<0.01), which was equivalent to 8 LT-RU per FL. The limiting dilution transplantation experiment showed that there was one functional hematopoietic stem cell out of 17 sorted SLAM cells in the control group, and one functional hematopoietic stem cell out of 39 sorted SLAM cells in the experimental group. The secondary transplantation experiments showed that 2 out of 4 recipients were reconstructed in the control group after 1 month, and 0 was reconstructed in the experimental group by transplanting 4×10 donor cells respectively. What's more, the percentage of S/G/M cells in the experimental group increased when compared with controls.@*CONCLUSION@#In the process of fetal liver hematopoiesis, the specifically knocking-out the Rictor in hematopoietic system can lead to defect of reconstitution ability, decrease of the functional hematopoietic stem cell numbers and reduction of self-renewal ability of hematopoietic stem cells.


Subject(s)
Animals , Fetus , Hematopoiesis , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Liver , Mice , Rapamycin-Insensitive Companion of mTOR Protein
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