STEM CELLS最新文献

{"title":"Decoding the Epigenetic and Transcriptional Basis of Direct Cardiac Reprogramming.","authors":"William G Peng, Anteneh Getachew, Yang Zhou","doi":"10.1093/stmcls/sxaf002","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf002","url":null,"abstract":"<p><p>Heart disease, particularly resulting from myocardial infarction (MI), continues to be a leading cause of mortality, largely due to the limited regenerative capacity of the human heart. Current therapeutic approaches seek to generate new cardiomyocytes from alternative sources. Direct cardiac reprogramming, which converts fibroblasts into induced cardiomyocytes (iCMs), offers a promising alternative by enabling in situ cardiac regeneration and minimizing tumorigenesis concerns. Here we review recent advancements in the understanding of transcriptional and epigenetic mechanisms underlying cardiac reprogramming, with a focus on key early-stage molecular events, including epigenetic barriers and regulatory mechanisms that facilitate reprogramming. Despite substantial progress, the maturation of reprogrammed iCMs and human cardiac fibroblast reprogramming remain areas for further exploration. We also discuss the combinatorial roles of reprogramming factors in governing transcriptional and epigenetic changes. This review consolidates current knowledge and proposes future directions for promoting the translational potential of cardiac reprogramming techniques.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Marrow Mononuclear Cell Transplantation Promotes Bone Healing via Gap Junction-Mediated Cell-Cell Interaction.","authors":"Yoshihito Suda, Akihiko Taguchi, Tomoyuki Matsumoto, Yuka Okinaka, Shinya Hayashi, Masanori Tsubosaka, Tomoyuki Kamenaga, Yuichi Kuroda, Naoki Nakano, Yuma Onoi, Shotaro Tachibana, Kensuke Wada, Akira Saito, Takuma Maeda, Shotaro Araki, Kohei Motono, Ryosuke Kuroda","doi":"10.1093/stmcls/sxae090","DOIUrl":"https://doi.org/10.1093/stmcls/sxae090","url":null,"abstract":"<p><strong>Aims: </strong>Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells that have been widely used in experimental therapies for patients with various diseases, including fractures.Activation of angiogenesis is believed to be one of the major modes of action of BM-MNCs; however, the essential mechanism by which BM-MNCs activate angiogenesis remains elusive. This study aimed to demonstrate that BM-MNCs promote bone healing by enhancing angiogenesis through direct cell-to-cell interactions via gap junctions, in addition to a previously reported method.</p><p><strong>Methods: </strong>Using a murine fracture model, we aimed to elucidate the relationship between gap junction-mediated cell-to-cell interactions and enhanced fracture healing after BM-MNC transplantation. We evaluated the transfer of substances from BM-MNCs to vascular endothelial cells and osteoblasts in the tissues surrounding the fracture site and assessed the effects of BM-MNC transplantation on bone healing, angiogenesis, and osteogenesis.</p><p><strong>Results: </strong>BM-MNCs transferred substances to vascular endothelial cells and osteoblasts in the tissues surrounding the fracture site. Moreover, BM-MNC transplantation promoted bone healing via gap junction-mediated cell-to-cell interactions, accelerating both angiogenesis and osteogenesis.</p><p><strong>Conclusions: </strong>Our findings provide a novel understanding of fracture healing mechanisms and suggest that BM-MNC transplantation enhances bone healing through gap junction-mediated cell-to-cell interactions, contributing to the development of regenerative medicine strategies targeting bone repair.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing approaches for targeted integration of transgenic cassettes by integrase-mediated cassette exchange in mouse and human stem cells.","authors":"Phalguni Rath, Philipp Kramer, Daniel Biggs, Chris Preece, Nicole Hortin, Rebeca Diaz, Marta Perez-Alcantara, Xiang Li, Arnaud Bolard, Nicola Beer, Mark McCarthy, Benjamin Davies","doi":"10.1093/stmcls/sxae092","DOIUrl":"10.1093/stmcls/sxae092","url":null,"abstract":"<p><p>To enable robust expression of transgenes in stem cells, recombinase-mediated cassette exchange at safe harbor loci is frequently adopted. The choice of recombinase enzyme is a critical parameter to ensure maximum efficiency and accuracy of the integration event. We have explored the serine recombinase family of site-specific integrases and have directly compared the efficiency of PhiC31, W-beta, and Bxb1 integrase for targeted transgene integration at the Gt(ROSA)26Sor locus in mouse embryonic stem cells. All 3 integrases were found to be suitable for efficient engineering and long-term expression of each integrase was compatible with pluripotency, as evidenced by germline transmission. Bxb1 integrase was found to be 2-3 times more efficient than PhiC31 and W-beta. The Bxb1 system was adapted for cassette exchange at the AAVS1 locus in human induced pluripotent stem (iPS) cells, and the 2 commonly used ubiquitous promoters, CAG and Ef1α (EIF1A), were tested for their suitability in driving expression of the integrated transgenic cargo. AAVS1-integrated Ef1α promoter led to a very mosaic pattern of expression in targeted hiPS cells, whereas the AAVS1-integrated CAG promoter drove consistent and stable expression. To validate the system for the integration of functional machinery, the Bxb1 integrase system was used to integrate CAG-driven CRISPR-activation and CRISPR-inhibition machinery in human iPS cells and robust sgRNA-induced up- and downregulation of target genes was demonstrated.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence Accelerated Mouse-Prone 8: a Model of Neuroinflammation and Aging with Features of Sporadic Alzheimer's disease.","authors":"Jun Ong, Kazunori Sasaki, Farhana Ferdousi, Megalakshmi Suresh, Hiroko Isoda, Francis G Szele","doi":"10.1093/stmcls/sxae091","DOIUrl":"https://doi.org/10.1093/stmcls/sxae091","url":null,"abstract":"<p><p>The large majority of Alzheimer's disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage of AD cases are familial, with known genetic causes. Paradoxically, there are only few validated mouse models of sporadic AD but many of familial AD. Senescence Accelerated Mouse-Prone 8 (SAMP8) mice are a model of accelerated aging with features of sporadic AD. They exhibit a more complete suite of human AD-relevant pathologies than most familial models. SAMP8 brains are characterized by inflammation, glial activation, β-amyloid deposits, and hyperphosphorylated Tau. The excess amyloid deposits congregate around blood vessels leading to vascular impairment and leaky BBBs in these mice. SAMP8 mice also exhibit neuronal cell death, a feature not typically seen in models of familial AD. Additionally, adult hippocampal neurogenesis is decreased in SAMP8 mice and correspondingly, they have reduced cognitive ability. In line with this, hippocampal LTP is significantly compromised in SAMP8 mice. No model is perfect and SAMP8 mice are limited by the lack of clarity about their genomic differences from control SAMR1 (Senescence Accelerated Mouse-Resistant 1) mice although their transcriptomics changes are being revealed. To further complicate matters, multiple substrains of SAMP8 mice have emerged over the years, sometimes making comparisons of studies difficult. Despite these challenges, we argue that SAMP8 mice can be useful for studying AD-relevant symptoms and propose important experiments to strengthen this already useful model.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 promotes osteogenesis by regulating N6-methyladenosine-dependent primary processing of hsa-miR-4526.","authors":"Yidan Song, Hongyu Gao, Yihua Pan, Yuxi Gu, Wentian Sun, Jun Liu","doi":"10.1093/stmcls/sxae089","DOIUrl":"https://doi.org/10.1093/stmcls/sxae089","url":null,"abstract":"<p><p>The function and mechanism of pri-miRNA N6-methyladenosine (m6A) modification in promoting miRNA maturation and regulating osteoblastic differentiation are not fully understood. The aim of this study was to investigate the role and regulatory mechanism of miRNA shear maturation regulated by methyltransferase like 3 (METTL3) in human adipose-derived stem cell (hASC) osteogenesis. Firstly, we found METTL3 promoted osteogenesis both in vivo and in vitro. Subsequently, three pri-miRNAs with the most significant methylated peaks were identified through methylated RNA immunoprecipitation sequencing (MeRIP-seq). Through quantitative real-time polymerase chain reaction (qRT-PCR), MeRIP-qPCR and co-immunoprecipitation (CO-IP), it was determined that METTL3 promoted the processing of hsa-miR-4526 by mediating pri-miR4526/5190 m6A modification. Subsequent in vivo and in vitro experiments demonstrated that hsa-miR-4526 promoted osteogenesis. Dual luciferase reporter assay was performed to verify that hsa-miR-4526 regulated osteogenic differentiation through TUBB3. It was found that TUBB3 can inhibit hASC osteogenesis. Further rescue experiments confirmed that METTL3 inhibited TUBB3 expression through hsa-miR-4526, thereby regulating osteogenic differentiation. RNA-seq revealed that TUBB3 may be involved in cell metabolism, calcium enrichment, osteoclast differentiation, and other pathways. Our study is the first to investigate the mechanism of pri-miRNA m6A modification in regulating hASC osteogenesis, presenting a novel idea and method for repairing bone defects.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes secreted from Amniotic mesenchymal stem cells modify trophoblast activities by delivering miR-18a-5p and regulating HRK-p53 interaction.","authors":"Wendi Zhao, Wenting Li, Jianxin Zuo, Huansheng Zhou, Guoqiang Gao, Yuanhua Ye, Yijing Chu","doi":"10.1093/stmcls/sxae087","DOIUrl":"https://doi.org/10.1093/stmcls/sxae087","url":null,"abstract":"<p><strong>Background: </strong>Amniotic mesenchymal stem cells (AMSCs) have been demonstrated as effective in tissue repair and regeneration. Trophoblast dysfunction is associated with several types of pregnancy complications. The aim of this study is to investigate the effects of AMSCs on the biological activities of human trophoblasts, as well as their molecular mechanisms.</p><p><strong>Methods: </strong>Exosomes were isolated from AMSC supernatants, and characterized and quantified by transmission electron microscopy (TEM) , nanoparticle tracking analysis (NTA) and Western blotting assay. Immunofluorescence assay was performed to detect the uptake of AMSCs-derived exomes (AMSC-Exos) by human trophoblasts. Human trophoblasts were subjected to transcriptome analysis after being co-cultured with AMSC-Exos. Lentiviral transfection was performed to construct the human trophoblast cell lines with stable HRK knockdown or overexpression. Immunohistochemistry was used to detect the HRK expression in preeclampsia (PE) patients. CCK8 and Transwell assays were respectively used to detect the trophoblast proliferation and migration. TUNEL flow cytometry assay was used to detect the apoptosis in trophoblasts. qRT-PCR and Western blotting assays were used to detect the mRNA and protein levels of the genes. Dual luciferase reporter assays were used to detect the changes in gene-transcript levels.</p><p><strong>Results: </strong>AMSC-Exos could be absorbed by human trophoblasts. Transcriptome analysis showed that HRK was significantly reduced in human trophoblasts co-cultured with AMSC-Exos. HRK inhibited cell proliferation and migration in human trophoblasts and promoted their apoptosis via p53 upregulation. miR-18a-5p, present at high levels in AMSC-Exos, improved trophoblast proliferation and migration, and inhibited their apoptosis by inhibiting the HRK expression.</p><p><strong>Conclusion: </strong>miR-18a-5p present in AMSC-Exos could be absorbed by trophoblasts, and in turn, improved their proliferation and migration and inhibited their apoptosis by HRK down-regulation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK cell cytotoxicity towards pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch.","authors":"Camilla Henden, Hege B Fjerdingstad, Elisabeth G Bjørnsen, Lavanya Thiruchelvam-Kyle, Michael R Daws, Marit Inngjerdingen, Joel C Glover, Erik Dissen","doi":"10.1093/stmcls/sxae083","DOIUrl":"https://doi.org/10.1093/stmcls/sxae083","url":null,"abstract":"<p><p>Pluripotent stem cells provide opportunities for treating injuries and previously incurable diseases. A major concern is the immunogenicity of stem cells and their progeny. Here, we have dissected the molecular mechanisms that allow natural killer (NK) cells to respond to human pluripotent stem cells, investigating a wide selection of activating and inhibitory NK cell receptors and their ligands. Reporter cells expressing the activating receptor NKG2D responded strongly to embryonic stem (ES) cell lines and induced pluripotent stem (iPS) cell lines, whereas reporter cells expressing the activating receptors NKp30, NKp46, KIR2DS1, KIR2DS2 and KIR2DS4 did not respond. Human ES and iPS cells invariably expressed several ligands for NKG2D. Expression of HLA-C and HLA-E was lacking or low, insufficient to trigger reporter cells expressing the inhibitory receptors KIR2DL1, -2DL2 or -2DL3. Similar results were obtained for the pluripotent embryonic carcinoma cell lines NTERA-2 and 2102Ep, and also iPS cell-derived neural progenitor cells. Importantly, neural progenitor cells and iPS cell-derived motoneurons also expressed B7H6, the ligand for the activating receptor NKp30. In line with these observations, IL-2 stimulated NK cells showed robust cytotoxic responses to ES and iPS cells as well as to iPS cell-derived motoneurons. No significant differences in cytotoxicity levels were observed between KIR/HLA matched and mismatched combinations of NK cells and pluripotent targets. Together, these data indicate that pluripotent stem cells and their neural progeny are targets for NK cell killing both by failing to sufficiently express ligands for inhibitory receptors and by expression of ligands for activating receptors.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Ablation of p16 Mitigates Premature Osteoporosis Induced by PTHrP Nuclear Localization Sequence and C-terminal Deletion through Inhibition of Cellular Senescence.","authors":"Yongli Han, Wanxin Qiao, Qi Xue, Dengshun Miao, Zhan Dong","doi":"10.1093/stmcls/sxae088","DOIUrl":"https://doi.org/10.1093/stmcls/sxae088","url":null,"abstract":"<p><p>Premature osteoporosis due to parathyroid hormone-related peptide (PTHrP) dysfunction presents significant bone health challenges. This study explores the role of p16-mediated cellular senescence in this condition using a Pthrp knock-in (KI) mouse model lacking the nuclear localization sequence and C-terminus of PTHrP. We generated p16⁻⁄⁻KI mice and compared them with wild-type, p16⁻⁄⁻, and KI mice. The genetic ablation of p16 in KI mice extended their lifespan, increased body size, and weight. Micro-CT analysis revealed a significant increase in bone volume, while histological and immunohistochemical studies revealed enhanced chondrocyte proliferation and osteoblast function in p16⁻⁄⁻KI mice. In vitro experiments showed enhanced differentiation capacity and reduced senescence of bone marrow mesenchymal stem cells (BM-MSCs) from p16⁻⁄⁻KI mice. Molecular analyses indicated that p16 knockout partially reversed oxidative stress, DNA damage, and cellular senescence observed in KI mice, as evidenced by upregulated antioxidant enzymes, reduced DNA damage markers, and decreased senescence markers. These findings highlight the critical role of p16-mediated cellular senescence in the premature osteoporosis phenotype of KI mice, suggesting that targeting cellular senescence pathways could offer a promising therapeutic strategy for premature osteoporosis and age-related bone loss. This research provides new insights into the interplay between genetic factors, cellular senescence, and bone metabolism in the context of aging and osteoporosis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in iPSC-Astrocyte morphology reflect Alzheimer's disease patient clinical markers.","authors":"Helen A Rowland, Georgina Miller, Qiang Liu, Shuhan Li, Nicola R Sharp, Bryan Ng, Tina Wei, Kanisa Arunasalam, Ivan Koychev, Anne Hedegaard, Elena M Ribe, Dennis Chan, Tharani Chessell, Ece Kocagoncu, Jennifer Lawson, Paresh Malhotra, Basil H Ridha, James B Rowe, Alan J Thomas, Giovanna Zamboni, Henrik Zetterberg, M Zameel Cader, Richard Wade-Martins, Simon Lovestone, Alejo Nevado-Holgado, Andrey Kormilitzin, Noel J Buckley","doi":"10.1093/stmcls/sxae085","DOIUrl":"https://doi.org/10.1093/stmcls/sxae085","url":null,"abstract":"<p><p>Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer's disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer's disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets. In this work iPSC-derived astrocytes were generated from a cohort of individuals with high versus low levels of the inflammatory marker YKL-40, in their cerebrospinal fluid (CSF). iPSC-derived astrocytes were treated with exogenous Aβ oligomers and high content imaging demonstrated a correlation between astrocytes that underwent the greatest morphology change from patients with low levels of CSF-YKL-40 and more protective APOE genotypes. This finding was subsequently verified using similarity learning as an unbiased approach. This study shows that iPSC-derived astrocytes from AD patients reflect key aspects of the pathophysiological phenotype of those same patients, thereby offering a novel means of modelling AD, stratifying AD patients and conducting therapeutic screens.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of 3 probiotics restores attenuated adult neurogenesis in germ-free mice.","authors":"Masakazu Namihira, Nana Inoue, Yohei Watanabe, Takuto Hayashi, Kazutoshi Murotomi, Kazuhiro Hirayama, Naoki Sato","doi":"10.1093/stmcls/sxae077","DOIUrl":"https://doi.org/10.1093/stmcls/sxae077","url":null,"abstract":"<p><p>Gut microbiota plays an important role in regulating brain function and adult neurogenesis. Although probiotics have recently been reported as effective against certain psychiatric disorders, the underlying mechanisms remain unclear. In particular, the combination of 3 probiotic strains, Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A, hereafter referred to as ProB3, has been reported to potentially alleviate psychiatric symptoms in patients with schizophrenia. Herein, we show that ProB3 promotes adult neurogenesis in mice and restores its dysregulation in germ-free (GF) mice. ProB3 colonization in GF mice enhanced the proliferation of adult neural stem cells compared to specific-pathogen-free and GF mice. Furthermore, ProB3 colonization was sufficient to ameliorate the arrest of newborn neuron maturation and the diminution of quiescent neural stem cells in GF mice. ProB3 colonization in mice increased the levels of several metabolites in the blood, including theanine and 3-hydroxybutyrate, and imidazole peptides, including anserine, which promoted proliferation, neurogenesis, and maturation of newborn neurons in cultured human fetus neural stem cells, as well as mouse adult hippocampal neural stem cells. Collectively, these results indicate that the essential role of the gut microbiota in adult hippocampal neurogenesis can be effectively complemented by the intake of a specific 3-strain probiotic, ProB3, providing novel insights into the brain-gut axis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}