STEM CELLS最新文献_第4页

MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy. msc来源的外泌体miR-125b-5p抑制糖尿病视网膜病变视网膜微血管内皮细胞铁下垂。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf023

Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie

{"title":"MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy.","authors":"Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie","doi":"10.1093/stmcls/sxaf023","DOIUrl":"10.1093/stmcls/sxaf023","url":null,"abstract":"Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956900","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

Unlocking the potential of regionally activated injury/ischemia-induced stem cells for neural regeneration. 释放区域激活损伤/缺血诱导干细胞用于神经再生的潜力。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf015

Takayuki Nakagomi

{"title":"Unlocking the potential of regionally activated injury/ischemia-induced stem cells for neural regeneration.","authors":"Takayuki Nakagomi","doi":"10.1093/stmcls/sxaf015","DOIUrl":"10.1093/stmcls/sxaf015","url":null,"abstract":"In the past, the mammal central nervous system (CNS) was assumed to lack the capacity for neural repair. However, increasing evidence shows that the CNS has repair capacity after injury. The migratory capacity of neural stem/progenitor cells (NSPCs) from subventricular zones (SVZ) is limited, and the precise repair mechanism active after ischemic stroke remains unknown. Consequently, it remains unclear how neural regeneration occurs in regions far from the SVZ, such as the cortex, especially given that these NSPCs can only migrate toward ischemic areas within specific brain regions. Nonetheless, using a mouse model of ischemic stroke with ischemic areas limited to the ipsilateral side of the cortex, we previously identified regionally-derived stem cells, injury/ischemia-induced stem cells (iSCs), within poststroke areas. Moreover, we showed that iSCs, which had the potential to differentiate into electrophysiologically functional neurons, were present within ischemic areas in poststroke human brains. This indicates that ischemic insult can activate locally-derived stem cells, even in nonneurogenic zones, and that iSCs can help achieve neural regeneration after ischemic stroke. However, inflammatory cells typically fill ischemic areas impairing neural regeneration in these areas. Here, we present the origin, characterization, and roles of iSCs based on our recent research. In addition, we discussed the potential of iSC-based therapies to achieve neural regeneration after ischemic stroke.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762665","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

CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells. CD44：肿瘤干细胞铁代谢、氧化还原平衡和治疗抵抗的关键调节因子

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf024

Taiju Ando, Juntaro Yamasaki, Hideyuki Saya, Osamu Nagano

{"title":"CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.","authors":"Taiju Ando, Juntaro Yamasaki, Hideyuki Saya, Osamu Nagano","doi":"10.1093/stmcls/sxaf024","DOIUrl":"10.1093/stmcls/sxaf024","url":null,"abstract":"CD44, a multifunctional cell surface protein, has emerged as a pivotal regulator in cancer stem cell (CSC) biology, orchestrating processes such as stemness, metabolic reprogramming, and therapeutic resistance. Recent studies have identified a critical role of CD44 in ferroptosis resistance by stabilizing SLC7A11 (xCT), a key component of the antioxidant defense system, enabling CSCs to evade oxidative stress and sustain tumorigenic potential. Additionally, CD44 regulates intracellular iron metabolism and redox balance, further supporting CSC survival and adaptation to stressful microenvironments. Therapeutic strategies targeting CD44, including ferroptosis inducers and combination therapies, have shown significant potential in preclinical and early clinical settings. Innovations such as CD44-mediated nanocarriers and metabolic inhibitors present novel opportunities to disrupt CSC-associated resistance mechanisms. Furthermore, the dynamic plasticity of CD44 isoforms governed by transcriptional, post-transcriptional, and epigenetic regulation underscores the importance of context-specific therapeutic approaches. This review highlights the multifaceted roles of CD44 in CSC biology, focusing on its contribution to ferroptosis resistance, iron metabolism, and redox regulation. Targeting CD44 offers a promising avenue for overcoming therapeutic resistance and improving the outcomes of refractory cancers. Future studies are needed to refine these strategies and enable their clinical translation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954716","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

ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation. ZIC1转录因子在节段性骨缺损中的过表达与棕色脂肪形成和成骨分化有关。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 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":"10.1093/stmcls/sxaf013","url":null,"abstract":"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 defects 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-SCIDγ mice. 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. The 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.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","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. 细胞疗法预防和治疗急性移植物抗宿主病。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 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":"10.1093/stmcls/sxaf009","url":null,"abstract":"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 (eg, naïve T-cells) without loss of T-cells with beneficial functions and retaining and/or enriching immune regulatory populations (eg, 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.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111709/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes. 炎症途径和骨髓微环境在遗传性骨髓衰竭综合征。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf021

Nicholas Neoman, Hye Na Kim, Jacob Viduya, Anju Goyal, Y Lucy Liu, Kathleen M Sakamoto

{"title":"Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes.","authors":"Nicholas Neoman, Hye Na Kim, Jacob Viduya, Anju Goyal, Y Lucy Liu, Kathleen M Sakamoto","doi":"10.1093/stmcls/sxaf021","DOIUrl":"10.1093/stmcls/sxaf021","url":null,"abstract":"Inherited bone marrow failure syndromes (IBMFS) are a diverse group of genetic disorders characterized by insufficient hematopoietic cell production due to blood stem cell dysfunction. The most common syndromes are Fanconi Anemia, Diamond-Blackfan Anemia, and Shwachman-Diamond Syndrome. These conditions share a theme of chronically producing pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, TGF-β, IFN-I, and IFN-γ. Each of these cytokines can impact the bone marrow microenvironment and drive the pathophysiology of IBMFS. This review aims to provide the latest progress in the field regarding the mechanistic underpinnings of inflammation in these IBMFS, as well as the effect of inflammation on the bone marrow microenvironment. A comprehensive understanding of the inflammation in IBMFS will open new avenues for intervention to restore bone marrow stability and improve patient prognosis. Future research must include targeting these mechanisms to develop novel therapies that can potentially mitigate the effects of chronic inflammation in IBMFS.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952420","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

Critical role of the potential O-linked glycosylation sites of CXCR4 in cell migration and bone marrow homing of hematopoietic stem progenitor cells. CXCR4潜在的o链糖基化位点在造血干细胞祖细胞的细胞迁移和骨髓归巢中的关键作用。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf025

Xuchi Pan, Chie Naruse, Tomoko Matsuzaki, Ojiro Ishibashi, Kazushi Sugihara, Hidetsugu Asada, Masahide Asano

引用次数: 0

Pdgfrβ marks distinct mesenchymal and pericyte populations within the periosteum with overlapping cellular features. Pdgfrβ标志着骨膜内不同的间充质和周细胞群体，具有重叠的细胞特征。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-15 DOI: 10.1093/stmcls/sxaf020

Ziyi Wang, Qizhi Qin, Neelima Thottappillil, Mario Gomez Salazar, Masnsen Cherief, Mary Archer, Deva Balaji, Aaron W James

{"title":"Pdgfrβ marks distinct mesenchymal and pericyte populations within the periosteum with overlapping cellular features.","authors":"Ziyi Wang, Qizhi Qin, Neelima Thottappillil, Mario Gomez Salazar, Masnsen Cherief, Mary Archer, Deva Balaji, Aaron W James","doi":"10.1093/stmcls/sxaf020","DOIUrl":"10.1093/stmcls/sxaf020","url":null,"abstract":"Platelet-derived growth factor receptor β (Pdgfrβ) is a cell surface marker often present on mesenchymal progenitor cells, playing a key role in regulating cell proliferation, migration, and survival. In the skeleton, Pdgfrβ-positive cells have significant osteogenic potential, differentiating into osteoblasts after injury to promote bone repair and homeostasis. However, multiple cell types within bone tissue express Pdgfrβ and their overlapping or distinct cellular features remain incompletely understood. Using a combination of single-cell RNA sequencing and transgenic Pdgfrβ-CreERT2-mT/mG reporter mice, we examined Pdgfrβ+ cells in mouse long bone periosteum. By single-cell analysis, Pdgfrb expression was found among a subset of mesenchymal cells and universally among pericytes within the periosteum. Histologic analysis of Pdgfrβ reporter activity confirmed a combination of perivascular and non-perivascular Pdgfrβ-expressing cell types. When isolated, Pdgfrβ reporter+ skeletal periosteal cells showed enhanced colony-forming, proliferative, migratory, and osteogenic capacities. Pdgfrβ reporter+ cells were further distinguished by co-expression of the pericyte marker CD146, which yielded Pdgfrβ+CD146+ pericytes and Pdgfrβ+CD146- skeletal mesenchymal cells. Colony forming and proliferative capacity were most highly enriched among Pdgfrβ+CD146+ pericytes, while osteogenic differentiation was similarly enriched across both Pdgfrβ+ cell fractions. In summary, Pdgfrβ expression identifies multiple subsets of progenitor cells within long bone periosteum with or without perivascular distribution and with overlapping cellular features.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951832","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

RUNX1 is a key inducer of human hematopoiesis controlling non-hematopoietic mesodermal development. RUNX1是人类造血控制非造血中胚层发育的关键诱导剂。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-15 DOI: 10.1093/stmcls/sxaf019

Zahir Shah, Cuihua Wang, Hanif Ullah, Hao You, Elena S Philonenko, Olga V Regan, Pavel Volchkov, Yong Dai, Jianhua Yu, Igor M Samokhvalov

{"title":"RUNX1 is a key inducer of human hematopoiesis controlling non-hematopoietic mesodermal development.","authors":"Zahir Shah, Cuihua Wang, Hanif Ullah, Hao You, Elena S Philonenko, Olga V Regan, Pavel Volchkov, Yong Dai, Jianhua Yu, Igor M Samokhvalov","doi":"10.1093/stmcls/sxaf019","DOIUrl":"10.1093/stmcls/sxaf019","url":null,"abstract":"The RUNX1/AML1 transcription factor is one of the key regulators of definitive hematopoietic development in mice. However, its role in early human hematopoiesis remains poorly investigated. In this study, we integrated a tdTomato reporter cassette into the RUNX1 locus of human pluripotent stem cells (hPSCs) to monitor and block the expression of the gene during hPSC differentiation. This approach demonstrated that expression of RUNX1 starts early in mesodermal specification focusing later on hemogenic endothelium (HE) and nascent hematopoietic cells. Lack of RUNX1 halted the development of CD43+ and CD235-CD45+ hematopoietic cells, preventing the production of clonogenic hematopoietic progenitors including the multilineage ones. The abrogation of RUNX1 resulted in the failure of definitive lineages, specifically T and NK cells. Remarkably, we instead observed the accumulation of RUNX1-null HE cells at the stage of blood cell generation. Moreover, the loss of the gene biased the development toward the lineage of CD43-CD146+CD90+CD73+ mesenchymal cells. RNA-seq analysis of RUNX1-null cells revealed the downregulation of top-level hematopoietic transcription factor genes and the reciprocal upregulation of genes associated with non-hematopoietic cells of mesodermal origin. Forced expression of RUNX1c in differentiating RUNX1-null hPSCs effectively rescued the development of CD45+ myeloid cells and megakaryocytes. Our data demonstrate that RUNX1 is a top hematopoietic inducer that simultaneously controls the expansion of non-hematopoietic lineages.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954424","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. 肾素祖细胞的命运是由血管紧张素1型受体信号在人肾类器官中调节的。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-15 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":"10.1093/stmcls/sxaf012","url":null,"abstract":"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 toward 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 a 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.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080355/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0