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ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-27 DOI: 10.1093/stmcls/sxaf013
Neelima Thottappillil, Zhao Li, Xin Xing, Shreya Arondekar, Manyu Zhu, Masnsen Cherief, Qizhi Qin, Myles Zhou, Mary Archer, Kristen Broderick, Bruno Pèault, Min Lee, Aaron W James
{"title":"ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation.","authors":"Neelima Thottappillil, Zhao Li, Xin Xing, Shreya Arondekar, Manyu Zhu, Masnsen Cherief, Qizhi Qin, Myles Zhou, Mary Archer, Kristen Broderick, Bruno Pèault, Min Lee, Aaron W James","doi":"10.1093/stmcls/sxaf013","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf013","url":null,"abstract":"<p><p>Transcriptional factor regulation is central to the lineage commitment of stem/ progenitor cells. ZIC1 (ZIC family member 1) is a C2H2-type zinc finger transcription factor expressed during development, brown fat, and certain cancers. Previously, we observed that overexpression of ZIC1 induces osteogenic differentiation at the expense of white adipogenic differentiation. In the present study, the feasibility of ZIC1 overexpressed human progenitor cells in critical sized bone defect was studied. To achieve this, human adipose stem/stromal cells with other without lentiviral ZIC1 overexpression were implanted in a femoral segmental defect model in NOD-SCIDγmice. Results showed that ZIC1 overexpressed cells induced osteogenic differentiation by protein markers in a critical sized femoral segment defect compared to empty lentiviral control, although bone union was not observed. Immunohistochemical evaluation showed that implantation of ZIC1 overexpression cells led to an increase in osteoblast antigen expression (RUNX2, OCN), activation of Hedgehog signaling (Patched1) and an increase in brown adipogenesis markers (ZIC1, EBF2). In contrast, no change in bone defect-associated vasculature was observed (CD31, Endomucin). Together, these data suggest that overexpression of the ZIC1 transcription factor in progenitor cells is associated with differentiation towards osteoblastic and brown adipogenic cell fates.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727129","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}
引用次数: 0
Cellular therapies for the prevention and treatment of acute graft-versus-host disease.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-21 DOI: 10.1093/stmcls/sxaf009
Daniel Peltier, Van Anh Do-Thi, Timothy Devos, Bruce R Blazar, Tomomi Toubai
{"title":"Cellular therapies for the prevention and treatment of acute graft-versus-host disease.","authors":"Daniel Peltier, Van Anh Do-Thi, Timothy Devos, Bruce R Blazar, Tomomi Toubai","doi":"10.1093/stmcls/sxaf009","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf009","url":null,"abstract":"<p><p>Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) that is caused by donor immune cells attacking and damaging host tissues. Immune suppressive small molecule and protein-based therapeutics targeting donor anti-host immune cells are currently used for GVHD prophylaxis and treatment. Even with these therapies, aGVHD progresses to life-threatening steroid-refractory aGVHD (SR-aGVHD) in up to 50% of cases and is a risk factor for the subsequent development of debilitating chronic GVHD. To improve aGVHD-related outcomes, donor graft engineering techniques and adoptive transfer of immune modulatory cells have been explored. Highly rigorous donor graft T-cell depletion approaches have revealed that mitigation of aGVHD can be accompanied by slow immune recovery post-allo-HCT and reduction in anti-microbial and anti-leukemia responses resulting in increased relapse and infection rates, respectively. Recent T-cell separation techniques allowing for precision graft engineering by selectively eliminating aGVHD-causing T-cells (e.g. naïve T-cells) without loss of T-cells with beneficial functions and retaining and/or enriching immune regulatory populations (e.g. regulatory T-cells (Tregs) or myeloid-derived suppressor cells) have been tested and will continue to improve. Clinical cell-based regulatory therapies have been employed for targeting SR-aGVHD, particularly mesenchymal stem cells (MSCs) and more recently, Tregs. In this review, we summarize aGVHD pathophysiology, highlight newly discovered aGVHD mechanisms, and discuss current and emerging cellular and graft manipulation approaches for aGVHD prevention and treatment.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672869","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}
引用次数: 0
Nephron progenitor fate is modulated by angiotensin type 1 receptor signaling in human kidney organoids.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-20 DOI: 10.1093/stmcls/sxaf012
Hyunjae Chung, Waleed Rahmani, Sarthak Sinha, Aysa Imanzadeh, Alexander Pun, Rohit Arora, Arzina Jaffer, Jeff Biernaskie, Justin Chun
{"title":"Nephron progenitor fate is modulated by angiotensin type 1 receptor signaling in human kidney organoids.","authors":"Hyunjae Chung, Waleed Rahmani, Sarthak Sinha, Aysa Imanzadeh, Alexander Pun, Rohit Arora, Arzina Jaffer, Jeff Biernaskie, Justin Chun","doi":"10.1093/stmcls/sxaf012","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf012","url":null,"abstract":"<p><p>The renin-angiotensin system (RAS) is essential for normal kidney development. Dysregulation of the RAS during embryogenesis can result in kidney abnormalities. To explore how angiotensin type 1 receptor (AT1R) signaling modulates nephron progenitor (NP) fate specification, we used induced pluripotent stem cell (iPSC) derived human kidney organoids treated with angiotensin II (Ang II) or the AT1R blocker losartan during differentiation. Ang II promoted NP proliferation and differentiation preferentially towards a podocyte fate, depleted the podocyte precursor population and accelerated glomerular maturation. By contrast, losartan expanded the podocyte precursor population, delayed podocyte differentiation and regressed the transcriptional signature to more immature fetal state. Overall, using various in silico approaches with validation by RNAscope, we identified a role for AT1R signaling in regulating NP fate during nephrogenesis in kidney organoids. Our work supports the use of RAS modulators to improve organoid maturation and suggests that RAS may be a determinant of nephron endowment in vivo.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661866","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}
引用次数: 0
SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-19 DOI: 10.1093/stmcls/sxaf010
Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho
{"title":"SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.","authors":"Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho","doi":"10.1093/stmcls/sxaf010","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf010","url":null,"abstract":"<p><p>SARS-CoV2, severe acute respiratory syndrome coronavirus 2, is frequently associated with neurological manifestations. Despite the presence of mild to severe CNS-related symptoms in a cohort of patients, there is no consensus whether the virus can infect directly brain tissue or if the symptoms in patients are a consequence of peripheral infectivity of the virus. Here, we use long-term human stem cell-derived cortical organoids to assess SARS-CoV2 infectivity of brain cells and unravel the cell-type tropism and its downstream pathological effects. Our results show consistent and reproducible low levels of SARS-CoV2 infection of astrocytes, deep projection neurons, upper callosal neurons and inhibitory neurons in 6 months human cortical organoids. Interestingly, astrocytes showed the highest infection rate among all infected cell populations that led to changes in their morphology and upregulation of SERPINA3, CD44 and S100A10 astrogliosis markers. Further, transcriptomic analysis revealed overall changes in expression of genes related to cell metabolism, astrogliosis and, inflammation and further, upregulation of cell survival pathways. Thus, local and minor infectivity of SARS-CoV2 in the brain may induce widespread adverse effects and lead to resilience of dysregulated neurons and astrocytes within an inflammatory environment.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655708","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}
引用次数: 0
Immunoregulatory iPSC-derived non-lymphoid progeny in autoimmunity and GVHD alloimmunity.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-19 DOI: 10.1093/stmcls/sxaf011
Lie Ma, Jordan Fink, Ke Yao, Cameron McDonald-Hyman, Phillip Dougherty, Brent Koehn, Bruce R Blazar
{"title":"Immunoregulatory iPSC-derived non-lymphoid progeny in autoimmunity and GVHD alloimmunity.","authors":"Lie Ma, Jordan Fink, Ke Yao, Cameron McDonald-Hyman, Phillip Dougherty, Brent Koehn, Bruce R Blazar","doi":"10.1093/stmcls/sxaf011","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf011","url":null,"abstract":"<p><p>Non-lymphoid immunoregulatory cells, including mesenchymal stem cells (MSCs), myeloid-derived suppressor cells (MDSCs), regulatory macrophages (Mregs), and tolerogenic dendritic cells (Tol-DCs), play critical roles in maintaining immune homeostasis. However, their therapeutic application in autoimmune diseases and graft-versus-host disease (GVHD) has received comparatively less attention. Induced pluripotent stem cells (iPSCs) offer a promising platform for cell engineering, enabling superior quality control, scalable production, and large-scale in vitro expansion of iPSC-derived non-lymphoid immunoregulatory cells. These advances pave the way for their broader application in autoimmune disease and GVHD therapy. Recent innovations in iPSC differentiation protocols have facilitated the generation of these cell types with functional characteristics akin to their primary counterparts. This review explores the unique features and generation processes of iPSC-derived non-lymphoid immunoregulatory cells, their therapeutic potential in GVHD and autoimmune disease, and their progress toward clinical translation. It emphasizes the phenotypic and functional diversity within each cell type and their distinct effects on disease modulation. Despite these advancements, challenges persist in optimizing differentiation efficiency, ensuring functional stability, and bridging the gap to clinical application. By synthesizing current methodologies, preclinical findings, and translational efforts, this review underscores the transformative potential of iPSC-derived non-lymphoid immunoregulatory cells in advancing cell-based therapies for alloimmune and autoimmune diseases.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655706","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}
引用次数: 0
Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson's disease.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-12 DOI: 10.1093/stmcls/sxaf004
Amalie Holm Nygaard, Alrik L Schörling, Zehra Abay-Nørgaard, Erno Hänninen, Yuan Li, Adrian Santonja, Gaurav Singh Rathore, Alison Salvador, Charlotte Rusimbi, Katrine Bech Lauritzen, Yu Zhang, Agnete Kirkeby
{"title":"Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson's disease.","authors":"Amalie Holm Nygaard, Alrik L Schörling, Zehra Abay-Nørgaard, Erno Hänninen, Yuan Li, Adrian Santonja, Gaurav Singh Rathore, Alison Salvador, Charlotte Rusimbi, Katrine Bech Lauritzen, Yu Zhang, Agnete Kirkeby","doi":"10.1093/stmcls/sxaf004","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf004","url":null,"abstract":"<p><p>Cell replacement therapies using human pluripotent stem cell-derived ventral midbrain (VM) dopaminergic (DA) progenitors are currently in clinical trials for treatment of Parkinson's disease (PD). Recapitulating developmental patterning cues, such as fibroblast growth factor 8 (FGF8), secreted at the midbrain-hindbrain boundary (MHB), is critical for the in vitro production of authentic VM DA progenitors. Here, we explored the application of alternative MHB-secreted FGF-family members, FGF17 and FGF18, for VM DA progenitor patterning. We show that while FGF17 and FGF18 both recapitulated VM DA progenitor patterning events, FGF17 induced expression of key VM DA progenitor markers at higher levels than FGF8 and transplanted FGF17-patterned progenitors fully reversed motor deficits in a rat PD model. Early activation of the cAMP pathway mimicked FGF17-induced patterning, although strong cAMP activation came at the expense of EN1 expression. In summary, we identified FGF17 as a promising alternative FGF candidate for robust VM DA progenitor patterning.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603087","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}
引用次数: 0
NK-cell cytotoxicity toward pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch. NK细胞对多能干细胞及其神经后代的细胞毒性:激活和抑制受体以及KIR/HLA错配的影响。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-10 DOI: 10.1093/stmcls/sxae083
Camilla Henden, Hege B Fjerdingstad, Elisabeth G Bjørnsen, Lavanya Thiruchelvam-Kyle, Michael R Daws, Marit Inngjerdingen, Joel C Glover, Erik Dissen
{"title":"NK-cell cytotoxicity toward 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":"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":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929945/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bone marrow mononuclear cell transplantation promotes bone healing via gap junction-mediated cell-cell interaction.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-10 DOI: 10.1093/stmcls/sxae090
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
{"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":"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>Bone marrow mononuclear cells 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":"2025-03-10","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}
引用次数: 0
Decoding the epigenetic and transcriptional basis of direct cardiac reprogramming.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-10 DOI: 10.1093/stmcls/sxaf002
William G Peng, Anteneh Getachew, Yang Zhou
{"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":"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, human cardiac fibroblast reprogramming and iCM maturation 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":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904897/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficient and rapid generation of neural stem cells by direct conversion of fibroblasts with single microRNAs.
IF 4 2区 医学
STEM CELLS Pub Date : 2025-03-10 DOI: 10.1093/stmcls/sxaf003
Yuanyuan Li, Jing Sun, Tingting Xu, Bo Dai, Yuesi Wang
{"title":"Efficient and rapid generation of neural stem cells by direct conversion of fibroblasts with single microRNAs.","authors":"Yuanyuan Li, Jing Sun, Tingting Xu, Bo Dai, Yuesi Wang","doi":"10.1093/stmcls/sxaf003","DOIUrl":"10.1093/stmcls/sxaf003","url":null,"abstract":"<p><p>Neural stem cells (NSCs) hold great potential in neurodegenerative disease therapy, drug screening, and disease modeling. However, current approaches for induced NSCs (iNSCs) generation from somatic cells are still slow and inefficient. Here we report the establishment of a rapid and efficient method of iNSCs generation from human and mouse fibroblasts by using single microRNAs (miR-302a). These iNSCs exhibited morphological, molecular and functional properties resembling those of adult human and mouse NSCs, respectively. Additionally, human iNSCs can be expanded for more than 20 passages in vitro. Furthermore, miR-302a alone was demonstrated to be sufficient to reprogram both human and mouse fibroblasts into iNSCs. Our results showed a method of direct conversion of autologous fibroblasts with miR-302a into iNSCs, providing a rapid and efficient strategy to generate iNSCs for both basic research and clinical applications.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035484","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}
引用次数: 0
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