Stem Cell ReportsPub Date : 2025-09-18DOI: 10.1016/j.stemcr.2025.102642
Tomohiro Mochida, Masato Miyoshi, Sei Kakinuma, Taro Shimizu, Jun Tsuchiya, Keiya Watakabe, Kento Inada, Shun Kaneko, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Mamoru Watanabe, Yasuhiro Asahina, Ryuichi Okamoto
{"title":"Crosstalk via ICAM-1 enhances supportive phenotype of stellate cells and drives hepatocyte proliferation in iPSC-derived hepatic organoids.","authors":"Tomohiro Mochida, Masato Miyoshi, Sei Kakinuma, Taro Shimizu, Jun Tsuchiya, Keiya Watakabe, Kento Inada, Shun Kaneko, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Mamoru Watanabe, Yasuhiro Asahina, Ryuichi Okamoto","doi":"10.1016/j.stemcr.2025.102642","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102642","url":null,"abstract":"<p><p>The interaction between hepatic stellate cells (HSCs) and hepatocytes contributes to HSC activation and liver regeneration; however, the mechanisms in humans remain unclear, particularly the significance of their direct contact and the role of cell adhesion molecules. In this study, we established a novel contact co-culture organoids using induced pluripotent stem cell (iPSC)-derived hepatic stellate-like cells (iPS-HSCs) and hepatocyte-like cells (iPS-Heps), termed iPSC-derived hepatocyte-stellate cell surrounding organoids (iHSOs). The iHSOs exhibit a unique morphology with iPS-HSCs surrounding central iPS-Heps. The iHSO enabled the identification of ICAM-1-interleukin-1β (IL-1β)-mediated iPS-Hep proliferation supported by iPS-HSCs, which displayed a quiescent and cytokine-rich phenotype, whereas this proliferative support was not observed in primary liver cell-based co-culture organoids. Furthermore, iHSOs treated with acetaminophen allowed for the modeling of HSC activation induced by hepatocyte injury, demonstrating their application potential. Our study presents a valuable platform for studying the HSC behavior and complex interactions between HSCs and hepatocytes in humans.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102642"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092464","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}
Stem Cell ReportsPub Date : 2025-09-18DOI: 10.1016/j.stemcr.2025.102643
Jonathan Jung, Nissim Benvenisty
{"title":"Drivers and implications of lineage-specific cancer-related mutations in human pluripotent and adult stem cells.","authors":"Jonathan Jung, Nissim Benvenisty","doi":"10.1016/j.stemcr.2025.102643","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102643","url":null,"abstract":"<p><p>Human pluripotent stem cells (PSCs) are known to harbor mutations in tumor-associated genes, and here we aim to examine the status of adult stem cells (ASCs). We thus identify cancer-related mutations in 18% of about 600 mesenchymal stem cell samples, and in 41% of about 200 neural stem cell (NSC) samples. We show a lineage-specific profile of cancer-related genes, demonstrating that TP53 is a central mutated gene in human PSCs but not in mesenchymal or NSCs. We suggest that the lineage-specificity of tumor-associated genes correlates with their expression levels and with tumor-specific mutations in patients. We also show the consequences of mutations in oncogenes and tumor suppressor genes on the transcriptome of each specific stem cell lineage. We therefore propose a categorization of these mutated samples for further appreciation of their severity and emphasize the importance of genetic screening in pluripotent and ASC lines.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102643"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092501","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":"Signaling pathway-based culture condition improves differentiation potential of canine induced pluripotent stem cells.","authors":"Toshiya Nishimura, Kazuto Kimura, Kyomi J Igarashi, Kohei Shishida, Hiroko Sugisaki, Masaya Tsukamoto, Aadhavan Balakumar, Chihiro Funamoto, Masumi Hirabayashi, Amir Kol, Shingo Hatoya","doi":"10.1016/j.stemcr.2025.102640","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102640","url":null,"abstract":"<p><p>Naturally occurring diseases in companion dogs are increasingly being recognized as valuable translational disease models. While induced pluripotent stem cell (iPSC) technology had revolutionized the field of human bio-medical research, canine iPSC (ciPSC) technology is still in its infancy, and robust canine-specific iPSC medium formulations and differentiation protocols are lacking. Here, we have established NANOG-reporter ciPSC lines and found that fibroblast growth factor (FGF), activin/transforming growth factor (TGF)-β, and WNT signals were critical for the robust maintenance of ciPSCs. Manipulating these signaling pathways stabilized the culture of ciPSC regardless of the cell line or basal medium. ciPSCs cultured in the optimized medium showed a homogenized global gene expression pattern. Furthermore, the ciPSCs cultured in this medium successfully differentiated into cardiomyocytes displaying homogenous contraction as well as sarcomere alignment. This robust culture condition provides a valuable resource to facilitate the utilization of ciPSCs for various studies, including human disease modeling.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102640"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092450","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}
Stem Cell ReportsPub Date : 2025-09-18DOI: 10.1016/j.stemcr.2025.102639
Chelsey J LeBlang, Maria F Pazyra-Murphy, Elizabeth S Silagi, Srestha Dasgupta, Marianna Tsolias, Toussaint Miller, Veselina Petrova, Shannon Zhen, Vukasin M Jovanovic, David Castellano, Kathryn Gerrish, Pinar Ormanoglu, Carlos A Tristan, Ilyas Singeç, Clifford J Woolf, Ozge Tasdemir-Yilmaz, Rosalind A Segal
{"title":"Satellite glial contact enhances differentiation and maturation of human iPSC-derived sensory neurons.","authors":"Chelsey J LeBlang, Maria F Pazyra-Murphy, Elizabeth S Silagi, Srestha Dasgupta, Marianna Tsolias, Toussaint Miller, Veselina Petrova, Shannon Zhen, Vukasin M Jovanovic, David Castellano, Kathryn Gerrish, Pinar Ormanoglu, Carlos A Tristan, Ilyas Singeç, Clifford J Woolf, Ozge Tasdemir-Yilmaz, Rosalind A Segal","doi":"10.1016/j.stemcr.2025.102639","DOIUrl":"10.1016/j.stemcr.2025.102639","url":null,"abstract":"<p><p>Sensory neurons generated from induced pluripotent stem cells (idSNs) are used to model human peripheral neuropathies; however, current differentiation protocols produce cells with an embryonic phenotype. Peripheral glia contact sensory neurons early in development and contribute to formation of the canonical pseudounipolar morphology, but these signals are not encompassed in current idSN differentiation protocols. Here, we show that terminal differentiation of idSNs in coculture with rat dorsal root ganglion (rDRG) satellite glia and glial precursors (rSG) advances differentiation and maturation. Cocultured idSNs develop pseudounipolar morphology through contact with rSG. In addition to morphological changes, idSNs terminally differentiated in coculture exhibit enhanced action potential firing, more mature gene expression, and increased susceptibility to paclitaxel-induced axonal degeneration. Thus, idSNs differentiated in coculture with rSG provide a better model for investigating human peripheral neuropathies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102639"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092407","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":"Unraveling the matrisome signatures of quiescent and activated muscle stem cells.","authors":"Emilie Guillon, Hisoilat Bacar, Laurent Gilquin, Takako Sasaki, Philippos Mourikis, Florence Ruggiero","doi":"10.1016/j.stemcr.2025.102635","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102635","url":null,"abstract":"<p><p>The extracellular matrix (ECM) forms a dynamic microenvironment, known as the \"niche,\" that influences muscle stem cell (MuSC) behavior. Its composition and topology remain underexplored. Using bioinformatics analysis of publicly available transcriptomic data, we profiled the matrisome of skeletal muscle-resident cells and identified quiescent MuSCs as key ECM producers. Their matrisome includes novel markers such as the basement membrane zone genes Col19a1 and Lama3, ECM assembly regulators Thsd4 and Aebp1, and notably, matrisome genes linked to neurogenesis. Light-sheet immunofluorescence microscopy of selected ECM components in isolated murine myofiber bundles revealed niche-specific ECM components associated with MuSCs. Upon activation, these cells shifted their gene expression, downregulating niche-associated ECM genes while upregulating those involved in basement membrane disruption and cell motility. These findings identify distinct matrisome signatures in quiescent and activated MuSCs, emphasizing the critical role of ECM in locally regulating MuSC states and highlighting its therapeutic potential for muscle regeneration.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102635"},"PeriodicalIF":5.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055952","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}
Stem Cell ReportsPub Date : 2025-09-09Epub Date: 2025-07-03DOI: 10.1016/j.stemcr.2025.102575
Sriivatsan G Rajan, Lynne M Nacke, Joseph N Lombardo, Farid Manuchehrfar, Kaelan Wong, Pinal Kanabar, Elizabeth A Somodji, Jocelyn Garcia, Mark Maienschein-Cline, Jie Liang, Ankur Saxena
{"title":"Progenitor neighborhoods function as transient niches to sustain olfactory neurogenesis.","authors":"Sriivatsan G Rajan, Lynne M Nacke, Joseph N Lombardo, Farid Manuchehrfar, Kaelan Wong, Pinal Kanabar, Elizabeth A Somodji, Jocelyn Garcia, Mark Maienschein-Cline, Jie Liang, Ankur Saxena","doi":"10.1016/j.stemcr.2025.102575","DOIUrl":"10.1016/j.stemcr.2025.102575","url":null,"abstract":"<p><p>Olfactory neurogenesis occurs throughout the lives of vertebrates, including in humans, and relies on the continuous differentiation and integration of neurons into a complex network. How progenitor cells convert fluctuations in cell-cell signaling into streamlined fate decisions over both space and time is poorly understood. Here, we track multicellular dynamics in the zebrafish olfactory epithelium, undertake targeted perturbations, and find that neurogenesis is driven by mutual antagonism between Notch signaling and insulinoma-associated 1a (Insm1a) that is responsive to inter-organ retinoic acid signaling. Single-cell analysis reveals that olfactory neurons emerge from transient groups of cells termed cellular neighborhoods. Stochastic modeling shows that neighborhood self-assembly is maintained by a tightly regulated bistable toggle switch. Differentiating cells migrate apically in response to brain-derived neurotrophic factor (BDNF) to take up residence as mature sensory neurons. Cumulatively, these findings reveal how stochastic signaling networks spatiotemporally regulate a balance between progenitors and derivatives, driving sustained neurogenesis in an intricate organ system.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102575"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565316","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}
Stem Cell ReportsPub Date : 2025-09-09Epub Date: 2025-08-21DOI: 10.1016/j.stemcr.2025.102606
Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić
{"title":"Computationally resolved neuroprogenitor cell biomarkers associate with human disorders.","authors":"Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić","doi":"10.1016/j.stemcr.2025.102606","DOIUrl":"10.1016/j.stemcr.2025.102606","url":null,"abstract":"<p><p>Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause Mendelian neurological conditions. In addition, leveraging a variety of computational tools and clinical and population databases, we identified 15 genes bearing novel damaging variants linked to neurological phenotypes, suggesting their potential role in contributing to human phenotypes. These discoveries illuminate NPC molecular underpinnings and underscore their relevance to both brain development and disease.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102606"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969807","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}
Stem Cell ReportsPub Date : 2025-09-09DOI: 10.1016/j.stemcr.2025.102630
Farah Alammari, Jemima Becker, Bin Sun, Anna Hoerder-Suabedissen, Keith W Vance, Francis G Szele
{"title":"The KAP1 chromatin regulator and Paupar long non-coding RNA control subventricular zone neural stem cell maintenance and neurogenesis.","authors":"Farah Alammari, Jemima Becker, Bin Sun, Anna Hoerder-Suabedissen, Keith W Vance, Francis G Szele","doi":"10.1016/j.stemcr.2025.102630","DOIUrl":"10.1016/j.stemcr.2025.102630","url":null,"abstract":"<p><p>Neural stem cells (NSCs) in the subventricular zone (SVZ) produce neurons throughout life. However, the epigenetic mechanisms that maintain NSCs and control neurogenesis remain unclear. We previously showed the long non-coding RNA (lncRNA) Paupar and KAP1 transcription co-factor control neuroblastoma cell growth. In the last stages of olfactory bulb (OB) neurogenesis, these two molecules affect rates of neurogenesis. Here we investigated upstream functions with inducible knockout and in vivo knockdown electroporation and molecular analysis. KAP1 and Paupar are expressed in the SVZ, physically interact in SVZ cells, and regulate NSC behavior. KAP1 directly maintains the NSC pool and regulates the expression of genes involved in the cell cycle. Paupar, in turn, maintains stem cell quiescence by restricting lineage progression from stem cells to transit amplifying progenitors (TAPs). These results suggest important roles for KAP1 and Paupar in the control of SVZ NSC maintenance and SVZ-OB neurogenesis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"20 9","pages":"102630"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034210","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}
Stem Cell ReportsPub Date : 2025-09-09Epub Date: 2025-08-14DOI: 10.1016/j.stemcr.2025.102600
Liying Chen, Zhongxia Li, Wenqi Wang, Yiting Zhou, Wenlu Li, Yi Wang
{"title":"Adult hippocampal neurogenesis: New avenues for treatment of brain disorders.","authors":"Liying Chen, Zhongxia Li, Wenqi Wang, Yiting Zhou, Wenlu Li, Yi Wang","doi":"10.1016/j.stemcr.2025.102600","DOIUrl":"10.1016/j.stemcr.2025.102600","url":null,"abstract":"<p><p>Neurogenesis, the biological process of forming new neurons, was traditionally believed to occur only during embryonic stages in the mammalian central nervous system for a long time. Over the past few decades, due to the development of new techniques and the accumulation of supportive evidence, adult neurogenesis is now accepted as the one of the most robust forms of plasticity in the adult brain, which contributes to physiological function as well as a range of neurological or psychiatric disorders. In this review, we mainly concentrate on adult neurogenesis in the hippocampus, the most likely neurogenic niche with significant roles in various brain functions. We begin by summarizing the current fundamental knowledge of adult hippocampal neurogenesis including proliferation, differentiation, maturation, and synapse formation of neural stem cells. We then focus on the potential roles of these adult-born neurons and their contribution to learning and memory behaviors and their relevance to various diseases. Furthermore, we review regulatory mechanisms governing adult hippocampal neurogenesis, including local environmental cues, multiple molecular signaling pathways, and neural network activities. We also discuss possible therapeutic strategies and targets that can be leveraged for future clinical translations. Finally, given the substantial progress in the field of regenerative medicine aimed at harnessing the multipotent resident cells for brain repair, we address remaining challenges and propose our perspectives on future directions for treating central nervous system disorders.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102600"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859616","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}
Stem Cell ReportsPub Date : 2025-09-09DOI: 10.1016/j.stemcr.2025.102613
Megumi Mizoguchi, Sebastian Jessberger, Yusaku Hontani
{"title":"Advances in intravital imaging of adult neurogenesis in mice.","authors":"Megumi Mizoguchi, Sebastian Jessberger, Yusaku Hontani","doi":"10.1016/j.stemcr.2025.102613","DOIUrl":"10.1016/j.stemcr.2025.102613","url":null,"abstract":"<p><p>The lifelong addition of stem-cell-derived neurons into distinct areas of the mammalian brain, such as the olfactory bulb and hippocampal dentate gyrus, provides structural and functional plasticity to neural circuits. To understand the dynamic processes underlying adult neurogenesis, from dividing stem/progenitor cells to integrating neurons, and to probe how new neurons shape brain function, intravital imaging turned out to be a powerful tool. Here, we review recent advances in the field of adult neurogenesis achieved by using in vivo imaging approaches in mice and discuss future directions of imaging-based experiments that will further our understanding of adult neurogenesis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"20 9","pages":"102613"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034133","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}