The nematode effector Mj-NEROSs interacts with Rieske's iron-sulfur protein influencing plastid ROS production to suppress plant immunity.

Root-knot nematodes (RKN; Meloidogyne species) are plant pathogens that introduce several effectors in their hosts to facilitate infection. The actual targets and functioning mechanism of these effectors largely remain unexplored. This study illuminates the role and interplay of the Meloidogyne javanica nematode effector ROS suppressor (Mj-NEROSs) within the host plant environment. Mj-NEROSs suppresses INF1-induced cell death as well as flg22-induced callose deposition and reactive oxygen species (ROS) production. A transcriptome analysis highlighted the downregulation of ROS-related genes upon Mj-NEROSs expression. NEROSs interacts with the plant Rieske's iron-sulfur protein (ISP) as shown by yeast-two-hybrid and bimolecular fluorescence complementation. Secreted from the subventral pharyngeal glands into giant cells, Mj-NEROSs localizes in the plastids where it interacts with ISP, subsequently altering electron transport rates and ROS production. Moreover, our results demonstrate that isp Arabidopsis thaliana mutants exhibit increased susceptibility to M. javanica, indicating ISP importance for plant immunity. The interaction of a nematode effector with a plastid protein highlights the possible role of root plastids in plant defense, prompting many questions on the details of this process.

Transcriptome Analysis of Meloidogyne javanica and the Role of a C-Type Lectin in Parasitism.

Meloidogyne javanica is one of the most widespread and economically important sedentary endoparasites. In this study, a comparative transcriptome analysis of M. javanica between pre-parasitic second-stage juveniles (Pre-J2) and parasitic juveniles (Par-J3/J4) was conducted. A total of 48,698 unigenes were obtained, of which 18,826 genes showed significant differences in expression (p < 0.05). In the differentially expressed genes (DEGs) from transcriptome data at Par-J3/J4 and Pre-J2, a large number of unigenes were annotated to the C-type lectin (CTL, Mg01965), the cathepsin L-like protease (Mi-cpl-1), the venom allergen-like protein (Mi-mps-1), Map-1 and the cellulase (endo-ß-1,4-glucanase). Among seven types of lectins found in the DEGs, there were 10 CTLs. The regulatory roles of Mj-CTL-1, Mj-CTL-2 and Mj-CTL-3 in plant immune responses involved in the parasitism of M. javanica were investigated. The results revealed that Mj-CTL-2 could suppress programmed cell death (PCD) triggered by Gpa2/RBP-1 and inhibit the flg22-stimulated ROS burst. In situ hybridization and developmental expression analyses showed that Mj-CTL-2 was specifically expressed in the subventral gland of M. javanica, and its expression was up-regulated at Pre-J2 of the nematode. In addition, in planta silencing of Mj-CTL-2 substantially increased the plant resistance to M. javanica. Moreover, yeast co-transformation and bimolecular fluorescence complementation assay showed that Mj-CTL-2 specifically interacted with the Solanum lycopersicum catalase, SlCAT2. It was demonstrated that M. javanica could suppress the innate immunity of plants through the peroxide system, thereby promoting parasitism.

A Bursaphelenchus xylophilus effector BxICD1 inducing plant cell death, concurrently contributes to nematode virulence and migration.

The migratory endoparasitic phytonematodes Bursaphelenchus xylophilus is the causal agent of pine wilt disease and causes significant economic damage to pine forests in China. Effectors play a key role in the successful parasitism of plants by phytonematodes. In this study, 210 genes obtained by transcriptomics analyses were found to be upregulated in B. xylophilus infecting Pinus massoniana that were not functionally annotated nor reported previously in B. xylophilus infecting P. thunbergii. Among these differentially expressed genes, a novel effector, BxICD1, that could induce cell death in the extracellular space of Nicotiana benthamiana was identified. BxICD1 was upregulated in the early stages of infection, as shown by RT-qPCR analyses. In situ hybridization analysis showed that BxICD1 was expressed in the esophageal gland of nematodes. The yeast signal sequence trap system indicated that BxICD1 possessed an N-terminal signal peptide with secretion functionality. Using an Agrobacterium-mediated transient expression system, it was demonstrated that the cell death-inducing activity of BxICD1 was dependent on N. benthamiana brassinosteroid-insensitive 1-associated kinase 1 (NbBAK1). Finally, BxICD1 contributed to B. xylophilus virulence and migration in host pine trees, as demonstrated by RNAi silencing assays. These findings indicate that BxICD1 both induces plant cell death and also contributes to nematode virulence and migration in P. massonian.

Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection.

BACKGROUND: Some bladder-related diseases, such as bladder urinary tract infection (UTI) and bladder cancer (BCa), have significant six differences in incidence and prognosis. However, the molecular mechanisms underlying these sex differences are still not fully understood. Understanding the sex-biased differences in gene expression in normal bladder cells can help resolve these problems. METHODS: We first collected published single-cell RNA sequencing (scRNA-seq) data of normal human bladders from females and males to map the bladder transcriptomic landscape. Then, Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were used to determine the significant pathways that changed in the specific cell populations. The Monocle2 package was performed to reconstruct the differentiation trajectories of fibroblasts. In addition, the scMetabolism package was used to analyze the metabolic activity at the single-cell level, and the SCENIC package was used to analyze the regulatory network. RESULTS: In total, 27,437 cells passed stringent quality control, and eight main cell types in human bladder were identified according to classical markers. Sex-based differential gene expression profiles were mainly observed in human bladder urothelial cells, fibroblasts, B cells, and T cells. We found that urothelial cells in males demonstrated a higher growth rate. Moreover, female fibroblasts produced more extracellular matrix, including seven collagen genes that may mediate BCa progression. Furthermore, the results showed that B cells in female bladders exhibited more B-cell activated signals and a higher expression of immunoglobulin genes. We also found that T cells in female bladders exhibited more T-cell activated signals. These different biological functions and properties of these cell populations may correlate with sex differences in UTI and BCa, and result in different disease processes and outcomes. CONCLUSIONS: Our study provides reasonable insights for further studies of sex-based physiological and pathological disparities in the human bladder, which will contribute to the understanding of epidemiological differences in UTI and BCa.

CRISPR/Cas9-mediated mutagenesis of the susceptibility gene OsHPP04 in rice confers enhanced resistance to rice root-knot nematode.

CRISPR crops carrying a mutation in susceptibility (S) genes provide an effective strategy for controlling plant disease, because they could be 'transgene-free' and commonly have more broad-spectrum and durable type of resistance. Despite their importance, CRISPR/Cas9-mediated editing of S genes for engineering resistance to plant-parasitic nematode (PPN) disease has not been reported. In this study, we employed the CRISPR/Cas9 system to specifically induce targeted mutagenesis of the S gene rice copper metallochaperone heavy metal-associated plant protein 04 (OsHPP04), and successfully obtained genetically stable homozygous rice mutants with or without transgenic elements. These mutants confer enhanced resistance to the rice root-knot nematode (Meloidogyne graminicola), a major plant pathogenic nematode in rice agriculture. Moreover, the plant immune responses triggered by flg22, including reactive oxygen species burst, defence-related genes expression and callose deposition, were enhanced in the 'transgene-free' homozygous mutants. Analysis of rice growth and agronomic traits of two independent mutants showed that there are no obvious differences between wild-type plants and mutants. These findings suggest that OsHPP04 may be an S gene as a negative regulator of host immunity and genetic modification of S genes through the CRISPR/Cas9 technology can be used as a powerful tool to generate PPN resistant plant varieties.

A spatiotemporal steroidogenic regulatory network in human fetal adrenal glands and gonads.

Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.

Corrigendum: Single-cell transcriptomics reveals the complexity of the tumor microenvironment of treatment-naive osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2021.709210.].

Single-Cell RNAseq Resolve the Potential Effects of LanCL1 Gene in the Mouse Testis.

Infertility affects lots of couples, half of which are caused by male factors. The LanCL1 gene is highly expressed in testis specifically, which might affect the development of sperms. In order to understand the potential functions of the LanCL1 gene in the testis, this study was conducted with constructed transgenic LanCL1 knockout mice. The mouse breeding experiment, semen analysis and single-cell RNAseq of testicular tissue were performed. Results suggested that the LanCL1 gene would significantly influence the reproduction ability and sperm motility of male mice. Single-cell RNAseq also confirmed the high expression of the LanCL1 gene in the spermatocytes and spermatids. Downregulating the LanCL1 gene expression could promote M2 macrophage polarity to maintain testicular homeostasis. Moreover, the LanCL1 gene could affect both the germ cells and stromal cells through various pathways such as the P53 signaling and the PPAR signaling pathway to disturb the normal process of spermatogenesis. However, no effects of the LanCL1 gene in testosterone synthesis and serum testosterone level were shown. Further studies are needed to discuss the mechanisms of the LanCL1 gene in the various cells of the testis independently.

A nematode effector inhibits plant immunity by preventing cytosolic free Ca2+ rise.

The Meloidogyne enterolobii effector MeTCTP is a member of the translationally controlled tumour protein (TCTP) family, involved in M. enterolobii parasitism. In this study, we found that MeTCTP forms homodimers and, in this form, binds calcium ions (Ca2+ ). At the same time, Ca2+ could induce homodimerization of MeTCTP. We further identified that MeTCTP inhibits the increase of cytosolic free Ca2+ concentration ([Ca2+ ]cyt ) in plant cells and suppresses plant immune responses. This includes suppression of reactive oxygen species burst and cell necrosis, further promoting M. enterolobii parasitism. Our results have elucidated that the effector MeTCTP can directly target Ca2+ by its homodimeric form and prevent [Ca2+ ]cyt rise in plant roots, revealing a novel mechanism utilized by plant pathogens to suppress plant immunity.

Single-cell transcriptomics reveals cell type diversity of human prostate.

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

Carcinogenic effect of adenylosuccinate lyase (ADSL) in prostate cancer development and progression through the cell cycle pathway.

BACKGROUND: Prostate cancer (PCa) is still a serious male malignant disease across the world. However, no exact pathogenesis had been explained. Although adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented. METHODS: The cBioPortal for Cancer Genomics, Oncomine and GEO database were retrieved to investigate the associations between of the ADSL gene and PCa. Then, the PC-3, DU145 and C4-2B cell lines were applied in vitro experiments. RNA sequencing and further western blot (WB) were applied to explore the potential mechanisms of ADSL gene in PCa. RESULTS: Based on PCa clinical datasets, we firstly found ADSL gene highly expressed in PCa tissues. Moreover, its transcript level increased in the metastatic PCa further. Elevated ADSL gene expression indicated a poor prognosis of PCa. While inhibiting the expression of ADSL with siRNA, the ability of cell proliferation and migration all declined markedly, with increased cell apoptosis inversely. Most of cells were blocked in the G0/G1 phase. Additionally, RNA sequencing also discovered the inactivity of cell cycle pathway after ADSL knockdown, which had also confirmed on the proteins levels. CONCLUSIONS: Our study identified the ADSL as an oncogene of PCa through regulating the cell cycle pathway firstly, with explicit cell and clinical phenotypes. Further mechanisms were needed to confirm its carcinogenic effect.

The Meloidogyne javanica effector Mj2G02 interferes with jasmonic acid signalling to suppress cell death and promote parasitism in Arabidopsis.

Plant-parasitic nematodes can cause devastating damage to crops. These nematodes secrete effectors that suppress the host immune responses to enhance their survival. In this study, Mj2G02, an effector from Meloidogyne javanica, is described. In situ hybridization and transcriptional analysis showed that Mj2G02 was highly expressed in the early infection stages and exclusively expressed in the nematode subventral oesophageal gland cells. In planta RNA interference targeting Mj2G02 impaired M. javanica parasitism, and Mj2G02-transgenic Arabidopsis lines displayed more susceptibility to M. javanica. Using an Agrobacterium-mediated transient expression system and plant immune response assays, we demonstrated that Mj2G02 localized in the plant cell nuclei and could suppress Gpa2/RBP-1-induced cell death. Moreover, by RNA-Seq and quantitative reverse transcription PCR analyses, we showed that Mj2G02 was capable of interfering with the host jasmonic acid (JA) signalling pathway. Multiple jasmonate ZIM-domain (JAZ) genes were significantly upregulated, whereas the JAR1 gene and four JA-responsive genes, MYC3, UPI, THI2.1, and WRKY75, were significantly downregulated. In addition, HPLC analysis showed that the endogenous jasmonoyl-isoleucine (JA-Ile) level in Mj2G02-transgenic Arabidopsis lines was significantly decreased compared to that in wildtype plants. Our results indicate that the M. javanica effector Mj2G02 suppresses the plant immune response, therefore facilitating nematode parasitism. This process is probably mediated by a JA-Ile reduction and JAZ enhancement to repress JA-responsive genes.

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

A new aphelench nematode, Basilaphelenchus brevistylus n. sp. (Aphelenchoididae: Tylaphelenchinae) from Pinus massoniana in China.

Basilaphelenchus brevistylus n. sp. was isolated from masson pine (Pinus massoniana) in Guangdong province, China. The new species is characterized by an offset lip region, short stylet (female stylet 4.5-5.5 µm and male stylet 4-5 µm long) with three elongate posteriorly directed knobs, posteriorly located metacorpal valve and lateral field composed of three lines. The female has an elongate postuterine sac and a short conical tail, uniformly narrowing toward a sharp tip, or tapering to a slightly offset mucronate tip in a few individuals. The male has a conical tail with a sharp terminal mucro, three pairs of caudal papillae, and small arcuate spicules with a bluntly rounded condylus and small pointed rostrum. B. brevistylus n. sp. can be distinguished from all described Basilaphelenchus nematodes by numerous morphological and morphometrical traits, especially the tail morphology of both sexes and stylet length. In addition, molecular phylogenetic trees inferred from rRNA small subunit and D2-D3 expansion domains of large subunit revealed that this nematode belongs to the Basilaphelenchus, and is clearly different from all the other Basilaphelsenchus species.

The Meloidogyne graminicola effector MgMO289 targets a novel copper metallochaperone to suppress immunity in rice.

Recent studies have reported that plant-parasitic nematodes facilitate their infection by suppressing plant immunity via effectors, but the inhibitory mechanisms remain poorly understood. This study found that a novel effector MgMO289 is exclusively expressed in the dorsal esophageal gland of Meloidogyne graminicola and is up-regulated at parasitic third-/fourth-stage juveniles. In planta silencing of MgMO289 substantially increased plant resistance to M. graminicola. Moreover, we found that MgMO289 interacts with a new rice copper metallochaperone heavy metal-associated plant protein 04 (OsHPP04), and that rice cytosolic COPPER/ZINC -SUPEROXIDE DISMUTASE 2 (cCu/Zn-SOD2) is the target of OsHPP04. Rice plants overexpressing OsHPP04 or MgMO289 exhibited an increased susceptibility to M. graminicola and a higher Cu/Zn-SOD activity, but lower O2•- content, when compared with wild-type plants. Meanwhile, immune response assays showed that MgMO289 could suppress host innate immunity. These findings reveal a novel pathway for a plant pathogen effector that utilizes the host O2•--scavenging system to eliminate O2•- and suppress plant immunity.

Single-cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment.

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.

A Meloidogyne graminicola Pectate Lyase Is Involved in Virulence and Activation of Host Defense Responses.

Plant-parasitic nematodes secrete an array of cell-wall-degrading enzymes to overcome the physical barrier formed by the plant cell wall. Here, we describe a novel pectate lyase gene Mg-PEL1 from M. graminicola. Quantitative real-time PCR assay showed that the highest transcriptional expression level of Mg-PEL1 occurred in pre-parasitic second-stage juveniles, and it was still detected during the early parasitic stage. Using in situ hybridization, we showed that Mg-PEL1 was expressed exclusively within the subventral esophageal gland cells of M. graminicola. The yeast signal sequence trap system revealed that it possessed an N-terminal signal peptide with secretion function. Recombinant Mg-PEL1 exhibited hydrolytic activity toward polygalacturonic acid. Rice plants expressing RNA interference vectors targeting Mg-PEL1 showed an increased resistance to M. graminicola. In addition, using an Agrobacterium-mediated transient expression system and plant immune response assays, we demonstrated that the cell wall localization of Mg-PEL1 was required for the activation of plant defense responses, including programmed plant cell death, reactive oxygen species (ROS) accumulation and expression of defense-related genes. Taken together, our results indicated that Mg-PEL1 could enhance the pathogenicity of M. graminicola and induce plant immune responses during nematode invasion into plants or migration in plants. This provides a new insight into the function of pectate lyases in plants-nematodes interaction.

Molecular Characterization of an Emerging Root-Knot Nematode Meloidogyne enterolobii in North Carolina, USA.

An emerging threat to agriculture, Meloidogyne enterolobii Yang & Eisenback, 1983, is a tropical species and considered to be the most damaging root-knot nematode (RKN) in the world because of its wide host range, aggressiveness, and ability to overcome resistance to RKN in many crops. It was first detected in the United States on ornamental plants in Florida in 2001 but has since been identified in North Carolina, South Carolina, and Louisiana. Several thousand RKN populations were collected from North Carolina field crops, ornamental plants, and turfgrasses for species identification in the Nematode Assay Laboratory in the North Carolina Department of Agriculture & Consumer Services. From 2006 to 2019, root systems showing galling symptoms were dissected under the microscope, and females were obtained for DNA analysis. When only soil samples were submitted, the second-stage juveniles or males were used instead. Molecular characterization was performed via polymerase chain reaction with species-specific primers and DNA sequencing on the ribosomal DNA 18S-ITS1-5.8S and 28S D2/D3 and mitochondrial DNA CoxII-16S. One hundred thirty-five representative RKN populations from North Carolina were characterized and identified as M. enterolobii. Six populations from China where the species was originally described were included in this study for identity confirmation and comparison. As of December 2019, M. enterolobii has been confirmed from a limited number of fields in 11 North Carolina counties: Columbus, Craven, Greene, Harnett, Johnston, Lenoir, Nash, Pitt, Sampson, Wayne, and Wilson. Currently, M. enterolobii is the most important emerging RKN species in the United States and causes severe damage to agronomic and horticultural crops, especially sweetpotato in North Carolina.

The Endogenous Alterations of the Gut Microbiota and Feces Metabolites Alleviate Oxidative Damage in the Brain of LanCL1 Knockout Mice.

Altered composition of the gut microbiota has been observed in many neurodegenerative diseases. LanCL1 has been proven to protect neurons and reduce oxidative stress. The present study was designed to investigate alterations of the gut microbiota in LanCL1 knockout mice and to study the interactions between gut bacteria and the brain. Wild-type and LanCL1 knockout mice on a normal chow diet were evaluated at 4 and 8-9 weeks of age. 16s rRNA sequence and untargeted metabolomics analyses were performed to investigate changes in the gut microbiota and feces metabolites. Real-time polymerase chain reaction analysis, AB-PAS staining, and a TUNEL assay were performed to detect alterations in the gut and brain of knockout mice. The serum cytokines of 9-week-old knockout mice, which were detected by a multiplex cytokine assay, were significantly increased. In the central nervous system, there was no increase of antioxidant defense genes even though there was only low activity of glutathione S-transferase in the brain of 8-week-old knockout mice. Interestingly, the gut tight junctions, zonula occludens-1 and occludin, also displayed a downregulated expression level in 8-week-old knockout mice. On the contrary, the production of mucus increased in 8-week-old knockout mice. Moreover, the compositions of the gut microbiota and feces metabolites markedly changed in 8-week-old knockout mice but not in 4-week-old mice. Linear discriminant analysis and t-tests identified Akkermansia as a specific abundant bacteria in knockout mice. Quite a few feces metabolites that have protective effects on the brain were reduced in 8-week-old knockout mice. However, N-acetylsphingosine was the most significant downregulated feces metabolite, which may cause the postponement of neuronal apoptosis. To further investigate the effect of the gut microbiota, antibiotics treatment was given to both types of mice from 5 to 11 weeks of age. After treatment, a significant increase of oxidative damage in the brain of knockout mice was observed, which may have been alleviated by the gut microbiota before. In conclusion, alterations of the gut microbiota and feces metabolites alleviated oxidative damage to the brain of LanCL1 knockout mice, revealing that an endogenous feedback loop mechanism of the microbiota-gut-brain axis maintains systemic homeostasis.

Single-cell profiling reveals sex diversity in human renal proximal tubules.

Many anatomical regions in the kidney, including proximal tubules, differ between males and females. While such differences in renal structures and functions under various physiological and pharmacological conditions have been identified, information relating to molecular mechanisms behind this gender disparity remain unknown. To understand gene expression differences in proximal tubules from human male and female kidneys, we reported on kidney cellular landscape using single-cell RNA sequencing. Differential gene expression profiles were observed in proximal tubules, between the sexes. Interestingly, the SLC22 family of anion transporters, including SLC22A6 and SLC22A8, had different expression profiles between male and female proximal tubule clusters but not sex-dependent abundance at the protein level. Moreover, in different species, we revealed a shared and species-specific differential gene expression between human and mouse kidney proximal tubules. Taken together, at single-cell resolution, this transcriptomic map represents a baseline description of gender biased genes in human kidney proximal tubules, which provide important insights for further studies of physiological differences in kidney.