Senescent Astrocytes Derived from Human Pluripotent Stem Cells Reveal Age-Related Changes and Implications for Neurodegeneration.

Astrocytes play a crucial role in maintaining brain homeostasis by regulating synaptic activity, providing metabolic support to neurons, and modulating immune responses in the central nervous system (CNS). During aging, astrocytes undergo senescence with various changes that affect their function and frequently lead to neurodegeneration. This study presents the first evidence of senescent astrocytes derived from human pluripotent stem cells (hPSCs). These senescent hPSC-derived astrocytes exhibited altered cellular and nuclear morphologies, along with increased expression of senescence-associated markers. Additionally, nuclear localization of NFκB, telomere shortening, and frequent signs of DNA damage were observed in these cells. Furthermore, senescent astrocytes showed defects in various critical functions necessary for maintaining a healthy CNS environment, including a reduced ability to support neuronal survival and clear neurotransmitters, synaptic debris, and toxic protein aggregates. Altered structural dynamics and reduced mitochondrial function were also observed in senescent astrocytes. Notably, treating hPSC-derived senescent astrocytes with chemicals targeting reactive oxygen species or an enzyme that regulates mitochondrial function can reverse senescence phenotypes. Thus, this study offers a valuable cellular model that can be utilized to investigate the mechanisms of brain aging and may present new avenues for discovering innovative therapeutic approaches for neurodegenerative diseases.

The complete chloroplast genome sequence and phylogenetic analysis of Asplenium antiquum Makino 1929, an Endangered species in Korea.

Asplenium antiquum Makino 1929 is one of the Endangered endemic species on the Korean Peninsula. The complete chloroplast of A. antiquum is 150,690 bp in length with typical quadripartite structure comprised of large single-copy region of (83,166 bp), a small single copy region (21,932 bp), and two inverted repeat regions, each 22,796 bp in length. 114 genes were detected in the chloroplast genome of A. antiquum, comprising 84 protein-encoding genes, 26 tRNA genes, and 4 rRNA genes. The phylogenetic analysis revealed a monophyletic relationship, placing A. antiquum as a sister to voth A. Prolongatum and A. nidus, forming a subclade of Asplenium species within the Aspleniaceae family. The genomic data obtained from this study will serve as valuable information for the species' genetic classification of Asplenium.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

In vitro comparison of the accuracy of an occlusal plane transfer method between facebow and POP bow systems in asymmetric ear position.

PURPOSE: This in vitro study aimed to compare the accuracy of the conventional facebow system and the newly developed POP (PNUD (Pusan National University Dental School) Occlusal Plane) bow system for occlusal plane transfer in asymmetric ear position. MATERIALS AND METHODS: Two dentists participated in this study, one was categorized as Experimenter 1 and the other as Experimenter 2 based on their clinical experience with the facebow (1F, 2F) and POP bow (1P, 2P) systems. The vertical height difference between the two ears of the phantom model was set to 3 mm. Experimenter 1 and Experimenter 2 performed the facebow and POP bow systems on the phantom model 10 times each, and the transfer accuracy was analyzed. The accuracy was evaluated by measuring the angle between the reference virtual plane (RVP) of the phantom model and the experimental virtual plane (EVP) of the upper mounting plate through digital superimposition. All data were statistically analyzed using a paired t-test (P < .05). RESULTS: Regardless of clinical experience, the POP bow system (0.53° ± 0.30 (1P) and 0.19° ± 0.18 (2P) for Experimenter 1 and 2, respectively) was significantly more accurate than the facebow system (1.88° ± 0.50 (1F) and 1.34° ± 0.25 (2F), respectively) in the frontal view (P < .05). In the sagittal view, no significant differences were found between the POP bow system (0.92° ± 0.50 (1P) and 0.73° ± 0.42 (2P) for Experimenter 1 and 2, respectively) and the facebow system (0.82° ± 0.49 (1F) and 0.60° ± 0.39 (2F), respectively), regardless of clinical experience (P > .05). CONCLUSION: In cases of asymmetric ear position, the POP bow system may transfer occlusal plane information more accurately than the facebow system in the frontal view, regardless of clinical experience.

The Effect of the Mixed Extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai on the Improvement of Degenerative Osteoarthritis through Inflammation Inhibition in the Monosodium Iodoacetate-Induced Mouse Model.

Osteoarthritis is a chronic inflammatory disease, and, due to the lack of fundamental treatment, the main objective is to alleviate pain and prevent cartilage damage. Kalopanax pictus Nakai and Achyranthes japonica Nakai are herbal plants known for their excellent anti-inflammatory properties. The objective of this study is to confirm the potential of a mixture extract of Kalopanax pictus Nakai and Achyranthes japonica Nakai as a functional raw material for improving osteoarthritis through anti-inflammatory effects in macrophages and MIA-induced arthritis experimental animals. In macrophages inflamed by lipopolysaccharide (LPS), treatment of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture inhibits NF-κB and mitogen-activated protein kinase (MAPK) activities, thereby inhibiting inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), inflammatory factors PGE2, MMP-2, and MMP-9, and nitric oxide (NO) was reduced. In addition, in an animal model of arthritis induced by MIA (monosodium iodoacetate), administration of Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture reduced blood levels of inflammatory cytokines TNF-α and IL-6, inflammatory factors prostaglandin E2(PGE2), matrix metalloproteinase-2(MMP-2), and NO. Through these anti-inflammatory effects, MIA-induced pain reduction (recovery of clinical index, increase in weight bearing, and increase in area and width of the foot), recovery of meniscus damage, loss of cartilage tissue or inflammatory cells in tissue infiltration reduction, and recovery of the proteglycan layer were confirmed. Therefore, it is considered that Kalopanax pictus Nakai and Achyranthes japonica Nakai mixture has the potential as a functional raw material that promotes joint health.

Differentiation of astrocytes with characteristics of ventral midbrain from human embryonic stem cells.

Molecular and functional diversity among region-specific astrocytes is of great interest in basic neuroscience and the study of neurological diseases. In this study, we present the generation and characterization of astrocytes from human embryonic stem cells with the characteristics of the ventral midbrain (VM). Fine modulation of WNT and SHH signaling during neural differentiation induced neural precursor cells (NPCs) with high expression of EN1 and NKX6.1, but less expression of FOXA2. Overexpression of nuclear factor IB in NPCs induced astrocytes, thereby maintaining the expression of region-specific genes acquired in the NPC stage. When cocultured with dopaminergic (DA) precursors or DA neurons, astrocytes with VM characteristics (VM-iASTs) promoted the differentiation and survival of DA neurons better than those that were not regionally specified. Transcriptomic analysis showed that VM-iASTs were more closely related to human primary midbrain astrocytes than to cortical astrocytes, and revealed the upregulation of WNT1 and WNT5A, which supports their VM identity and explains their superior activity in DA neurons. Taken together, we hope that VM-iASTs can serve to improve ongoing DA precursor transplantation for Parkinson's disease, and that their transcriptomic data provide a valuable resource for investigating regional diversity in human astrocyte populations.

Humulus japonicus Extract Ameliorates Hepatic Steatosis Through the PPARα-Mediated Suppression of Alcohol-Induced Oxidative Stress.

Humulus japonicus has been used to treat obesity, hypertension, and nonalcoholic fatty liver and to alleviate inflammation and oxidative stress. In the present study, we aimed to investigate the effects of H. japonicus ethanol extracts (HE) and luteolin 7-O-ß-d-glucoside (LU), which is identified as a major active component of H. japonicus, on ethanol-induced oxidative stress and lipid accumulation in primary hepatocytes. Mouse primary hepatocytes were treated with HE and stimulated with ethanol. The MTT test was used to determine cell viability. By using Western blotting, the effects of HE on the expression of different proteins were investigated. Experimental mice were given a 5% alcohol liquid Lieber-DeCarli diet to induce alcoholic fatty liver. We found that both HE and LU individually attenuated ethanol-induced lipid accumulation, lipogenic protein expression, and cellular oxidative stress in hepatocytes. Treatment with HE or LU increased PPARα and SOD1 expression and catalase activity in a dose-dependent manner. Small interfering RNA of PPARα reduced the effects of HE on oxidative stress, lipid metabolism, and levels of antioxidants. We also observed that orally administered HE treatment alleviated hepatic steatosis in a diet containing ethanol-fed mice. This study suggests HE as a functional food that can improve hepatic steatosis, thereby preventing hepatic injury caused by alcohol consumption.

Three cases of jejunal tumors detected by standard upper gastrointestinal endoscopy: A case series.

BACKGROUND: In patients with obscure gastrointestinal bleeding, re-examination with standard upper endoscopes by experienced physicians will identify culprit lesions in a substantial proportion of patients. A common practice is to insert an adult-sized forward-viewing endoscope into the second part of the duodenum. When the endoscope tip enters after the papilla, which is a marker for the descending part of the duodenum, it is difficult to endoscopically judge how far the duodenum has been traversed beyond the second part. CASE SUMMARY: We experienced three cases of proximal jejunal masses that were diagnosed by standard upper gastrointestinal endoscopy and confirmed with surgery. The patients visited the hospital with a history of melena; during the initial upper gastrointestinal endoscopy and colonoscopy, the bleeding site was not confirmed. Upper gastrointestinal bleeding was suspected; thus, according to guidelines, upper endoscopy was performed again. A hemorrhagic mass was discovered in the small intestine. The lesion of the first patient was thought to be located in the duodenum when considering the general insertion depth of a typical upper gastrointestinal endoscope; however, during surgery, it was confirmed that it was in the jejunum. After the first case, lesions in the second and third patients were detected at the jejunum by inserting the standard upper endoscope as deep as possible. CONCLUSION: The deep insertion of standard endoscopes is useful for the diagnosis of obscure gastrointestinal bleeding.

Bile Acids: Major Regulator of the Gut Microbiome.

Bile acids are synthesized from cholesterol and play an important role in regulating intestinal microflora. The different degrees of hydrophobicity and acidity of individual bile acids may affect their antimicrobial properties. We examined the antimicrobial effects of different bile acids on various microorganisms in vitro and confirmed whether these remain consistent in vivo. Using human bile acids, including ursodeoxycholic acid, cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, a disc diffusion test was performed, and a rodent model was created to determine the antimicrobial effects of each bile acid. The fecal bacterial population was analyzed using a real-time polymerase chain reaction. Each bile acid showed different microbial inhibitory properties. The inhibitory activity of bile acids against microbiota which normally resides in the gastrointestinal tract and biliary system, was low; however, normal flora of other organs was significantly inhibited. Changes in microbial counts after bile acid administration in a rodent model differed in the colon and cecum. The in vivo and in vitro results show that the antimicrobial effects of bile acids against intestinal microbiota were similar. In conclusion, bile acids could be a novel treatment strategy to regulate gut microbiota.

Generation of mutation-corrected induced pluripotent stem cell lines derived from adrenoleukodystrophy patient by using homology directed repair.

X-linked adrenoleukodystrophy (ALD) caused by the ABCD1 mutation, is the most common inherited peroxisomal disease. Previously, we generated an ALD patient-derived SCHi001-A iPSC model. In this study, we have performed the first genome editing of ALD patient-derived SCHi001-A iPSCs using homology-directed repair (HDR). The mutation site, c.1534G > A [GenBank: NM_000033.4], was corrected by introducing ssODN and the CRISPR/Cas9 system. The cell line exhibited normal iPSC plulipotency marker expression following genome editing. Mutation-corrected iPSCs from SCHi001-A iPSC line can be used in research into the pathophysiology of and therapeutics for ALD.

OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease.

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5+ (an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4+ iOPCs was similar to that of O4+ OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes. Notably, engrafted iOPCs remyelinated the brains of adult shiverer mice and experimental autoimmune encephalomyelitis mice with MOG-induced 14 weeks after transplantation. In conclusion, our study may contribute to the development of therapeutic approaches for neurological disorders, as well as facilitate the understanding of the molecular mechanisms underlying glial development.

Trophoblast glycoprotein is a new candidate gene for Parkinson's disease.

Parkinson's disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12-14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.

A Novel Vitronectin Peptide Facilitates Differentiation of Oligodendrocytes from Human Pluripotent Stem Cells (Synthetic ECM for Oligodendrocyte Differentiation).

Differentiation of oligodendrocytes (ODs) presents a challenge in regenerative medicine due to their role in various neurological diseases associated with dysmyelination and demyelination. Here, we designed a peptide derived from vitronectin (VN) using in silico docking simulation and examined its use as a synthetic substrate to support the differentiation of ODs derived from human pluripotent stem cells. The designed peptide, named VNP2, promoted OD differentiation induced by the overexpression of SOX10 in OD precursor cells compared with Matrigel and full-length VN. ODs differentiated on VNP2 exhibited greater contact with axon-mimicking nanofibers than those differentiated on Matrigel. Transcriptomic analysis revealed that the genes associated with morphogenesis, cytoskeleton remodeling, and OD differentiation were upregulated in cells grown on VNP2 compared with cells grown on Matrigel. This new synthetic VN-derived peptide can be used to develop a culture environment for efficient OD differentiation.

Blackcurrant Improves Diabetic Cardiovascular Dysfunction by Reducing Inflammatory Cytokines in Type 2 Diabetes Mellitus Mice.

Diabetic cardiovascular dysfunction is a representative complication of diabetes. Inflammation associated with the onset and exacerbation of type 2 diabetes mellitus (T2DM) is an essential factor in the pathogenesis of diabetic cardiovascular complications. Diabetes-induced myocardial dysfunction is characterized by myocardial fibrosis, which includes structural heart changes, myocardial cell death, and extracellular matrix protein accumulation. The mice groups in this study were divided as follows: Cont, control (db/m mice); T2DM, type 2 diabetes mellitus mice (db/db mice); Vil.G, db/db + vildagliptin 50 mg/kg/day, positive control, dipeptidyl peptidase-4 (DPP-4) inhibitor; Bla.C, db/db + blackcurrant 200 mg/kg/day. In this study, Bla.C treatment significantly improved the homeostatic model evaluation of glucose, insulin, and insulin resistance (HOMA-IR) indices and diabetic blood markers such as HbA1c in T2DM mice. In addition, Bla.C improved cardiac function markers and cardiac thickening through echocardiography. Bla.C reduced the expression of fibrosis biomarkers, elastin and type IV collagen, in the left ventricle of a diabetic cardiopathy model. Bla.C also inhibited TD2M-induced elevated levels of inflammatory cytokines in cardiac tissue (IL-6, IL-1ß, TNF-α, and TGF-ß). Thus, Bla.C significantly improved cardiac inflammation and cardiovascular fibrosis and dysfunction by blocking inflammatory cytokine activation signals. This showed that Bla.C treatment could ameliorate diabetes-induced cardiovascular complications in T2DM mice. These results provide evidence that Bla.C extract has a significant effect on the prevention of cardiovascular fibrosis, inflammation, and consequent diabetes-induced cardiovascular complications, directly or indirectly, by improving blood glucose profile.

YG-1 Extract Improves Acute Pulmonary Inflammation by Inducing Bronchodilation and Inhibiting Inflammatory Cytokines.

YG-1 extract used in this study is a mixture of Lonicera japonica, Arctic Fructus, and Scutellariae Radix. The present study was designed to investigate the effect of YG-1 extract on bronchodilatation (ex vivo) and acute bronchial and pulmonary inflammation relief (in vivo). Ex vivo: The bronchodilation reaction was confirmed by treatment with YG-1 concentration-accumulation (0.01, 0.03, 0.1, 0.3, and 1 mg/mL) in the bronchial tissue ring pre-contracted by acetylcholine (10 µM). As a result, YG-1 extract is considered to affect bronchodilation by increased cyclic adenosine monophosphate, cAMP) levels through the ß2-adrenergic receptor. In vivo: experiments were performed in C57BL/6 mice were divided into the following groups: control group; PM2.5 (fine particulate matter)-exposed group (PM2.5, 200 µg/kg/mL saline); and PM2.5-exposed + YG-1 extract (200 mg/kg/day) group. The PM2.5 (200 µg/kg/mL saline) was exposed for 1 h for 5 days using an ultrasonic nebulizer aerosol chamber to instill fine dust in the bronchi and lungs, thereby inducing acute lung and bronchial inflammation. From two days before PM2.5 exposure, YG-1 extract (200 mg/kg/day) was administered orally for 7 days. The PM2.5 exposure was involved in airway remodeling and inflammation, suggesting that YG-1 treatment improves acute bronchial and pulmonary inflammation by inhibiting the inflammatory cytokines (NLRP3/caspase-1 pathway). The application of YG-1 extract with broncho-dilating effect to acute bronchial and pulmonary inflammation animal models has great significance in developing therapeutic agents for respiratory diseases. Therefore, these results can provide essential data for the development of novel respiratory symptom relievers. Our study provides strong evidence that YG-1 extracts reduce the prevalence of respiratory symptoms and the incidence of non-specific lung diseases and improve bronchial and lung function.

Highly sensitive self-healable strain biosensors based on robust transparent conductive nanocellulose nanocomposites: Relationship between percolated network and sensing mechanism.

The conventional skin sensor detection of human physiological signals can be an effective method for disease diagnosis and health monitoring, but the poor biocompatibility, low sensitivity and complex design largely limit their applications. Developing natural nanofiller-reinforced composites as strain biosensors is an appealing solution to reduce environmental impacts and overcome technical bottleneck. Herein, a versatile nature skin-inspired composite film as flexible strain biosensor was developed based on cellulose nanocrystals-polyaniline (CNC-PANI) composites by utilizing their percolated conductive network in polyvinyl alcohol (PVA) matrix. The composite electronic skin showed robust mechanical strength (50.62 MPa) and high sensitivity (Gauge Factor = 11.467) with easy water-induced self-healing abilities. Moreover, we investigated the functioning mechanism of percolated network and the sensory behavior determined by CNC nanocomposite alignment. The percolation threshold of CNC-polyaniline (PANI) was determined at 4.278% and 5% CNC-PANI composite film shows the best overall sensing property. It was also discovered that the sensitivity of this type of conductive-filler electronic skin can be divided into two separate regions at different strain range due to its percolated network. With films prepared by dry casting and dip coating, the alignment of CNC-PANI also contributes to this unique change in electrical property. Generally, our results demonstrated the mechanism and tunability of conductive nanofiller-based composite strain biosensors as a potential alternative to commercial synthetic sensors.

Trophoblast glycoprotein is a marker for efficient sorting of ventral mesencephalic dopaminergic precursors derived from human pluripotent stem cells.

Successful cell therapy for Parkinson's disease (PD) requires large numbers of homogeneous ventral mesencephalic dopaminergic (vmDA) precursors. Enrichment of vmDA precursors via cell sorting is required to ensure high safety and efficacy of the cell therapy. Here, using LMX1A-eGFP knock-in reporter human embryonic stem cells, we discovered a novel surface antigen, trophoblast glycoprotein (TPBG), which was preferentially expressed in vmDA precursors. TPBG-targeted cell sorting enriched FOXA2+LMX1A+ vmDA precursors and helped attain efficient behavioral recovery of rodent PD models with increased numbers of TH+, NURR1+, and PITX3+ vmDA neurons in the grafts. Additionally, fewer proliferating cells were detected in TPBG+ cell-derived grafts than in TPBG- cell-derived grafts. Our approach is an efficient way to obtain enriched bona fide vmDA precursors, which could open a new avenue for effective PD treatment.

Influence of Non-Thermal Atmospheric Pressure Plasma Treatment on Retentive Strength between Zirconia Crown and Titanium Implant Abutment.

The aim of this study is to investigate the effect of non-thermal atmospheric pressure plasma (NTP) on retentive strength (RS) between the zirconia crown and the titanium implant abutment using self-adhesive resin cement. Surface free energy (SFE) was calculated on 24 cube-shaped zirconia blocks, and RS was measured on 120 zirconia crown-titanium abutment assemblies bonded with G-CEM LinkAce. The groups were categorized according to the zirconia surface treatment as follows: Control (no surface treatment), NTP, Si (Silane), NTP + Si, Pr (Z-Prime Plus), and NTP + Pr. Half of the RS test assemblies were aged by thermocycling for 5000 cycles at 5-55 °C. The SFE was calculated using the Owens-Wendt method, and the RS was measured using a universal testing machine at the maximum load until failure. One-way analysis of variance (ANOVA) with post-hoc Tukey honestly significant difference (HSD) was performed to evaluate the effect of surface treatments on the SFE and RS. Independent sample t-test was used to compare the RS according to thermocycling (p < 0.05). For the SFE analysis, the NTP group had a significantly higher SFE value than the Control group (p < 0.05). For the RS test, in non-thermocycling, the NTP group showed a significantly higher RS value than the Control group (p < 0.05). However, in thermocycling, there was no significant difference between the Control and NTP groups (p > 0.05). In non-thermocycling, comparing with the NTP + Si or NTP + Pr group, there was no significant difference from the Si or Pr group, respectively (p > 0.05). Conversely, in thermocycling, the NTP + Si and NTP + Pr group had significantly lower RS than the Si and Pr group, respectively (p < 0.05). These results suggest that NTP single treatment for the zirconia crown increases the initial RS but has little effect on the long-term RS. Applied with Silane or Z-Prime Plus, NTP pre-treatment has no positive effect on the RS.

NFIB induces functional astrocytes from human pluripotent stem cell-derived neural precursor cells mimicking in vivo astrogliogenesis.

The ability to generate astrocytes from human pluripotent stem cells (hPSCs) offers a promising cellular model to study the development and physiology of human astrocytes. The extant methods for generating functional astrocytes required long culture periods and there remained much ambiguity on whether such paradigms follow the innate developmental program. In this report, we provided an efficient and rapid method for generating physiologically functional astrocytes from hPSCs. Overexpressing the nuclear factor IB in hPSC-derived neural precursor cells induced a highly enriched astrocyte population in 2 weeks. RNA sequencing and functional analyses demonstrated progressive transcriptomic and physiological changes in the cells, resembling in vivo astrocyte development. Further analyses substantiated previous results and established the MAPK pathway necessary for astrocyte differentiation. Hence, this differentiation paradigm provides a prospective in vitro model for human astrogliogenesis studies and the pathophysiology of neurological diseases concerning astrocytes.