Stem Cell Reports最新文献

{"title":"Establishing mouse forebrain organoids as models of intrinsic cortical network assembly.","authors":"Sebastian Hernandez, Hunter E Schweiger, Isabel Cline, Gregory A Kaurala, Ash Robbins, Daniel Solis, Samira Vera-Choqqueccota, Jinghui Geng, Tjitse van der Molen, Francisco Reyes, Chinweike Norman Asogwa, Kateryna Voitiuk, Mattia Chini, Marco Rolandi, Sofie R Salama, Bradley M Colquitt, Tal Sharf, David Haussler, Mircea Teodorescu, Mohammed A Mostajo-Radji","doi":"10.1016/j.stemcr.2026.102832","DOIUrl":"10.1016/j.stemcr.2026.102832","url":null,"abstract":"<p><p>The mouse cortex is a canonical model for studying how functional neural networks emerge, yet it remains unclear which topological features arise from intrinsic cellular organization versus sensory input. Mouse forebrain organoids provide a powerful system to investigate these intrinsic mechanisms. We generated dorsal (DF) and ventral (VF) forebrain organoids from mouse pluripotent stem cells and tracked their development using longitudinal electrophysiology. DF organoids showed progressively stronger network-wide correlations, while VF organoids developed more refined activity patterns with enhanced small-world topology and increased modular organization. Both organoid types form small-world networks, but their topological organization differs. These differences emerge without extrinsic inputs and correlate with Pvalb⁺ interneuron enrichment in VF organoids. Our findings demonstrate how cellular composition influences neural circuit self-organization, establishing mouse forebrain organoids as a tractable platform to study cortical network architecture.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102832"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370328","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":"Myosin VB is critical for progenitor cell identity and function in the intestine.","authors":"Andreanna Burman, Monica E Brown, Yilin Yang, Michael Momoh, Francisca Adeniran, Cynthia Ramos, Ken S Lau, Linda C Samuelson, Mitchell D Shub, Joseph T Roland, Izumi Kaji","doi":"10.1016/j.stemcr.2026.102862","DOIUrl":"10.1016/j.stemcr.2026.102862","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102862"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356433","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":"Messenger RNA delivery into Sertoli cells restores fertility to congenitally infertile male mice.","authors":"Mito Kanatsu-Shinohara, Narumi Ogonuki, Shogo Matoba, Takehiro Miyazaki, Hiroko Morimoto, Tianjiao Liu, Naoto Yoshinaga, Atsuo Ogura, Satoshi Uchida, Takashi Shinohara","doi":"10.1016/j.stemcr.2026.102829","DOIUrl":"10.1016/j.stemcr.2026.102829","url":null,"abstract":"<p><p>Male infertility often results from impaired interactions between germ cells and Sertoli cells. While in vitro fertilization and intracytoplasmic sperm injection are widely used, their success depends on the presence of haploid germ cells. Gene therapy remains challenging due to concerns about germline transmission. The mRNA offers a safer option, as its short-life reduces this risk. Here, we show that mRNA delivery into mouse testes restores fertility in a genetic model of infertility. Injected mRNA was specifically expressed in Sertoli cells; although it triggered an innate immune response, spermatogenesis resumed without major side effects. Delivery of naked Cldn11 mRNA into Cldn11-deficient mice, which have meiotic defects due to defective blood-testis barrier, allowed progression from spermatocytes to spermatids. Fertile offspring with normal imprinting were produced via microinsemination. These findings demonstrate the potential of mRNA-based therapy for treating male infertility by targeting testicular somatic cells, without introducing genetic material into the germline.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102829"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370455","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":"Toward standardized iPSC testing: Insights from a multi-year international Quality Assessment Round.","authors":"Alice Hägg, Rachel Wood, Ayako L Mochizuki, Keren Abberton, Elsa Abranches, Belén Alvarez-Palomo, Ricardo Baptista, Raiana Andrade Quintanilha Barbosa, Jacqueline Barry, Adriana Bastos Carvalho, Annelise Bennaceur Griscelli, Antonio Carlos Campos de Carvalho, Diana Chaker, Hong Chang, Hye Young Choi, Margarita Codinach, Begoña Arán Corbella, Scott Cowan, Sarah Jane Dickerson, Ngaire Elwood, Xueling Fan, Maxime Feyeux, Maddy Forrester, Andrew Gaffney, Solenn M Guilbert, Hye-Yeong Ha, Adam J Hirst, Arwen L Hunter, Leanne G Jamieson, Robert N Judson, Yonehiro Kanemura, Tais Hanae Kasai-Brunswick, Jung-Hyun Kim, Howard Kim, Manisha Kintali, Siddharth Krishnan, Bernd Kuebler, Chui Yu Lau, Wilson Li, Amanda Mack, Michael R MacLeod, Marinna Madrid, Hiroaki Mamiya, Lucie Manache-Alberici, Dragoş Mărginean, Olivier Mentre, Stefanie L Morgan, Joanne Mountford, Humayun Munir, Siemon H S Ng, Haruna Ogawa, Steve Oh, Hidetaka Ohara, Keiko Oono, Niall Park, Lygia V Pereira, Izabella Pereira da Silva Bezerra, Alexandru Robert Podovei, Sergio Querol, Jainy Raje, Angel Raya, Satoko Sakamoto, Raquel Sarafian, Kathleen Schmit, Silvia Selvitella, Gurbind Singh, Matthew J K Smart, Jihwan Song, Glyn Stacey, Stephen Sullivan, Miho Sumida, Cecile Terrenoire, Pei Tian, Elias Uhlin, José M A Vaquero, Anna Veiga, Jar Wei Vicky Wang, Katherine Warre-Cornish, Jamie Wood, Atsuyo Yamamoto, Gaojun Zhang, Takafusa Hikichi, Marc Turner, Anna Falk","doi":"10.1016/j.stemcr.2026.102857","DOIUrl":"10.1016/j.stemcr.2026.102857","url":null,"abstract":"<p><p>Despite rapid clinical translation, induced pluripotent stem cell (iPSC)-derived therapies face limited global adoption. Harmonized quality control (QC) remains absent, with even fundamental parameters evaluated inconsistently across laboratories. To address this, we conducted two international Quality Assessment Rounds (QARs): QAR 2019 (18 sites, 11 countries) and QAR 2023 (23 sites, 12 countries), evaluating flow cytometry-based assessment of the undifferentiated state and qPCR-based genomic integrity testing. QAR 2019 showed high consistency in genomic integrity testing, while uncovering substantial variability in flow cytometry, prompting QAR 2023 to introduce standardized workflows. These improvements enabled systematic, cross-site evaluation of marker performance across cell states, identifying OCT3/4, TRA-1-60, and SSEA5 as consistently robust pluripotency-associated markers. This global benchmarking effort provides the first empirical multi-site evidence for reproducible iPSC QC and marker-level reliability. Together, these findings establish a foundation for harmonized QC supporting interoperable iPSC banks, regulatory alignment, and scalable manufacturing of globally accessible regenerative therapies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102857"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491739","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":"Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.","authors":"Dayoung Kim, Takayuki Kondo, Haruhisa Inoue","doi":"10.1016/j.stemcr.2026.102866","DOIUrl":"10.1016/j.stemcr.2026.102866","url":null,"abstract":"<p><p>Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss. Microglia, the brain's resident macrophages, are key contributors to disease pathogenesis, with many genetic risk variants enriched in microglia-specific genes. While rodent models have provided valuable insights, human induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) technologies now enable the generation of human microglia-like cells, offering a physiologically relevant platform to study human microglial biology. This review discusses the developmental origins and functions of microglia, current differentiation approaches, and how these models help elucidate disease-relevant phenotypes and molecular mechanisms in neurodegeneration.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102866"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147532624","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":"Genome-edited safe and immune-evasive human pluripotent cells: Potential solution for allogeneic therapies.","authors":"Vivian Tam, Nicole Ching Man Wong, Andrew Chung Hin Poon, Mengxia Zhu, Ting Mei, Janette Kwok, Patrick Chu, Eric D Jong, Jean Kit Tang, Andras Nagy, Danny Chan","doi":"10.1016/j.stemcr.2026.102850","DOIUrl":"10.1016/j.stemcr.2026.102850","url":null,"abstract":"<p><p>We used an embryonic stem cell line (H1) engineered for immune-evading properties to avoid rejection (\"AlloAccept\") and equipped with a \"SafeCell\" (SC) kill-switch to eliminate aberrantly proliferating cells. Utilizing a humanized immune system mouse model, we demonstrated the successful generation of allogeneic tissues from SafeCell-AlloAccept (SC-AlloAccept) cells in immunocompetent humanized mice in the immune-active subcutaneous region. These cells formed various tissue types, and their growth can be controlled with pro-drug ganciclovir to activate the kill switch, which eliminated proliferating cells and rendered the remaining tissue dormant. Strikingly, SC-AlloAccept-derived grafts survived for 5 months, underscoring their potential for long-term engraftment. Importantly, neither prior rejection of immunogenic parental H1 cells (sensitization) nor the presence of immune-evasive H1-derived tissue (potential immunocompromising) affected the immune response to a subsequent second transplant. This study validated the utility of SC-AlloAccept human cells in transplantation and enhanced the safety and efficacy of stem cell-based regenerative therapies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102850"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370371","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":"New legal category of 'advanced regenerative medicine treatment' in Korea's amended regenerative medicine law: comparative lessons from Japan.","authors":"Jinah Yoon, Sukhyang Lee, Jung-Hyun Kim","doi":"10.1016/j.stemcr.2026.102852","DOIUrl":"10.1016/j.stemcr.2026.102852","url":null,"abstract":"<p><p>South Korea's Act on the Safety of and Support for Advanced Regenerative Medicine and Advanced Biological Products, enacted in 2019, was recently amended. This article examines the new advanced regenerative medicine treatment (ARMT) category, focusing on patient access, review processes, safety monitoring, ethical safeguards, and lessons from Japan's comparable framework.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102852"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459851","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":"Diversity of cortical progenitors directs neuronal layer formation and regional glial patterning.","authors":"Ana Cristina Ojalvo-Sanz, María Figueres-Oñate, Sonsoles Barriola, Carolina Pernia-Solanilla, Rebeca Sanchez-Gonzalez, Lina M Delgado-García, Laura López-Mascaraque","doi":"10.1016/j.stemcr.2026.102855","DOIUrl":"10.1016/j.stemcr.2026.102855","url":null,"abstract":"<p><p>How distinct cortical progenitor types and their temporal differences influence neuronal and glial development remains a key question in neurobiology. While radial glial cells (RGCs) are well-established as neural progenitors (NPCs), NG2⁺NPCs have emerged as contributors with unique characteristics. Here, we combined in utero electroporation, lineage tracing and transcriptomic profiling to compare lineage outputs of NG2⁺ and GFAP⁺ NPCs in the developing mouse cortex. Both generate neurons and glia, but with partially distinct patterns in lineage output, spatial distribution, and fate bias. NG2⁺ NPCs undergo an early neurogenic phase followed by glial differentiation, producing glia with laminar distribution biases. In contrast, GFAP⁺ NPCs sustain neurogenesis longer, producing a broader range of neurons and more constant glia during development. Our findings highlight the contribution of progenitor identity and temporal differences to distinct, partially overlapping lineage trajectories, supporting a model in which fate potential and timing co-regulate the spatial and laminar organization of cortical cell types.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102855"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491729","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":"Deuterosomal cells are the responsible lineage for multiciliogenesis in human airway differentiation.","authors":"Haruka Yamaki, Satoshi Konishi, Koji Tamai, Naoyuki Sone, Senye Takahashi, Yifei Xu, Takahiro Tsuji, Hiroaki Ozasa, Takuya Yamamoto, Toyohiro Hirai, Kazuhiko Takeuchi, Shimpei Gotoh","doi":"10.1016/j.stemcr.2026.102860","DOIUrl":"10.1016/j.stemcr.2026.102860","url":null,"abstract":"<p><p>Multiciliated cells (MCCs) are pivotal in airway defense via their motile cilia to eliminate inhaled pathogens and particles. Genetic variants in primary ciliary dyskinesia (PCD) disrupt ciliary function, resulting in chronic respiratory infections. The formation of MCCs requires centriole amplification mediated by non-membranous organelles called deuterosomes, whose regulatory mechanisms remain poorly characterized in humans. Single-cell transcriptomic analyses have identified \"deuterosomal cells\" (DCs), a transient cell population that emerges during multiciliogenesis. DCs are challenging to investigate owing to their scarcity. To elucidate the role of DCs, iPSC-derived airway epithelial cells were used to identify CD36 as a specific surface marker. Furthermore, iPSCs were established from a patient with PCD harboring Cyclin O (CCNO) variants, along with gene-corrected controls. Patient-derived iPSCs demonstrated defective MCC differentiation and aberrant DCs attributed to CCNO deficiency. This study provides a human iPSC-based platform for investigating the mechanisms underlying airway multiciliogenesis and PCD modeling.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102860"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491765","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":"Dose-resolved control of somatic reprogramming by Rora.","authors":"Haiyun Wang, Yusha Li, Chunkou Yin, Zhen Zhang, Yixuan Wang, Yi Li, Chuang Li, Runxia Lin, Xiaoli Zhang, Jing Guo, Rongping Luo, Shumin Li, Lv Zhang, Yingting Zhuang, Anchun Xu, Jiani Wan, Lizhan Xiao, Bailing Chen, Shengyong Yu, Manish Kumar, Jing Liu","doi":"10.1016/j.stemcr.2026.102870","DOIUrl":"10.1016/j.stemcr.2026.102870","url":null,"abstract":"<p><p>Nuclear receptors (NRs) are ligand-regulated transcription factors whose domains and dosage modulate gene networks. We systematically profiled 49 murine NRs in OKS (OCT4/KLF4/SOX2) reprogramming of mouse fibroblasts and identified the ROR subfamily as enhancers. Focusing on Rora, we uncovered a dose-dependent, biphasic effect on reprogramming: moderate Rora increases OCT4-GFP⁺ colony formation, whereas higher expression reduces colonies. Domain dissection separated these arms-DNA-binding domain (DBD)/ligand-binding domain (LBD) was required for the pro-reprogramming effect, while the N-terminal domain (NTD) was required for high-dose inhibition (ΔNTD eliminated the inhibitory limb). Functionally, the reprogramming barrier interferon (IFN)-γ was attenuated at transcript and protein levels; IFN-γ add-back dampened the enhancement, supporting immune-axis modulation. Conversely, WNT pathway output was reduced in the inhibitory arm, and CHIR99021 partially rescued the high-dose colony defect. Thus, RORA acts as a dose-programmed, domain-modular regulator that coordinates chromatin and signaling to gate cell-fate conversion, establishing nuclear-receptor dosage control as a lever to improve reprogramming efficiency.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102870"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616763","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}