STEM CELLS最新文献_第2页

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

Transcriptomic Analysis of the m6A Reader YTHDF2 in the Maintenance and Differentiation of Human Embryonic Stem Cells. m6A读取器YTHDF2在人胚胎干细胞维持和分化中的转录组学分析。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-26 DOI: 10.1093/stmcls/sxaf032

Boshi Feng, Yanxi Chen, Huanchang Tu, Jin Zhang, Lingling Tong, Xiaohan Lyu, Aaron Trent Irving, Di Chen

{"title":"Transcriptomic Analysis of the m6A Reader YTHDF2 in the Maintenance and Differentiation of Human Embryonic Stem Cells.","authors":"Boshi Feng, Yanxi Chen, Huanchang Tu, Jin Zhang, Lingling Tong, Xiaohan Lyu, Aaron Trent Irving, Di Chen","doi":"10.1093/stmcls/sxaf032","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf032","url":null,"abstract":"As the most abundant internal modification on mRNAs, N6-methyladenosine (m6A) has been discovered to be involved in different biological processes. Mostly determined by m6A methyl-transferases (m6A writers) and demethylases (m6A erasers), different cell types possess differential m6A profiles of transcriptomes. However, the interpretation of the m6A-encoded epitranscriptomic information needs m6A readers to bind and recruit different machinery for regulating the target mRNAs, which in turn, may regulate cell fates. The functions of the m6A readers in the regulation of the maintenance and differentiation of human embryonic stem cells (hESCs) remain largely unknown. In this study, we deleted the whole genomic region of the m6A reader YTHDF2 and discovered that YTHDF2 is dispensable for the maintenance, but important for the differentiation of hESCs, especially for the differentiation towards ectoderm. Furthermore, we identified the m6A-modified ROBO1 mRNAs as potential targets by YTHDF2 in regulating hESC to neuroectoderm differentiation. This study reveals the potential roles of the m6A reader YTHDF2 in regulating the specification of neuroectodermal cell fate.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148896","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

Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury. 干细胞CNTF促进嗅觉上皮神经再生和损伤后功能恢复。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-22 DOI: 10.1093/stmcls/sxaf033

Derek Cox, Brian Wang, Joe Oliver, Jaeden Pyburn, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia

{"title":"Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury.","authors":"Derek Cox, Brian Wang, Joe Oliver, Jaeden Pyburn, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia","doi":"10.1093/stmcls/sxaf033","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf033","url":null,"abstract":"Olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) are continuously replaced by neuroregeneration from basal stem cells. Acute inflammation destroys OSNs, causing hyposmia or anosmia, but leaves the basal stem cells intact. We previously found that ciliary neurotrophic factor (CNTF) is highly expressed in horizontal basal cells (HBCs) and the CNTF receptor is in globose basal cells (GBCs), which are the actively dividing cells that normally replace dying OSNs. Here, we investigated the role of CNTF in basal stem cell proliferation/differentiation and smell function recovery following methimazole-induced acute inflammatory OE injury. Methimazole increased inflammatory markers, TNFα, IL-6, and CD45, and depleted OSNs in the OE at 3 and 5 days. Simultaneously, CNTF and the GBC marker Mash1 were upregulated, suggesting that HBCs produced more CNTF, as validated using primary HBC cultures, to promote GBC proliferation. Methimazole increased GBC proliferation, as shown by the number of BrdU-labeled GBCs in CNTF+/+, but not in CNTF-/- littermate mice. Also, CNTF+/+ mice had higher levels of neuroregeneration and better smell function recovery than CNTF-/- littermates. This indicates that CNTF promotes GBC proliferation and promotes OE neuroregeneration and smell functional recovery. This study identifies the regenerative role of CNTF in HBCs and reveals the therapeutic potential to target CNTF signaling to improve olfactory neuroregeneration and functional recovery following injury.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118493","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

Rabbit Induced Pluripotent Stem Cells -Derived Mesenchymal Stem Cells for Enhanced Wound Healing. 兔诱导多能干细胞衍生间充质干细胞促进伤口愈合。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-16 DOI: 10.1093/stmcls/sxaf028

Hsing-Yi Yu, Yang-Zhe Huang, Edward Chern

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

In Reply to Letter to the Editor from Paudel: Comment on "Changes in iPSC-Astrocyte Morphology Reflect Alzheimer's Disease Patient Clinical Markers". 回复pauldel给编辑的信：关于“ipsc -星形细胞形态变化反映阿尔茨海默病患者临床标志物”的评论。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-15 DOI: 10.1093/stmcls/sxaf031

Noel J Buckley, Helen A Rowland

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

Renal protective effects of extracellular vesicle-encapsulated tumor necrosis factor-α-induced protein 6 derived from mesenchymal stem cells. 间充质干细胞细胞外囊泡包膜肿瘤坏死因子-α-诱导蛋白6的肾保护作用。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-15 DOI: 10.1093/stmcls/sxaf022

Keisuke Morimoto, Ayumu Nakashima, Naoki Ishiuchi, Kisho Miyasako, Yoshiki Tanaka, Kensuke Sasaki, Go Matsuda, Satoshi Maeda, Shigeru Miyaki, Takao Masaki

{"title":"Renal protective effects of extracellular vesicle-encapsulated tumor necrosis factor-α-induced protein 6 derived from mesenchymal stem cells.","authors":"Keisuke Morimoto, Ayumu Nakashima, Naoki Ishiuchi, Kisho Miyasako, Yoshiki Tanaka, Kensuke Sasaki, Go Matsuda, Satoshi Maeda, Shigeru Miyaki, Takao Masaki","doi":"10.1093/stmcls/sxaf022","DOIUrl":"10.1093/stmcls/sxaf022","url":null,"abstract":"Acute kidney injury (AKI) is involved in subsequent chronic kidney disease (CKD) development, and effective treatments to prevent AKI to CKD progression are lacking. Mesenchymal stem cells (MSCs) are emerging as a promising cellular therapy to impede such progression through the secretion of various humoral factors. Among these factors, tumor necrosis factor-α-induced protein 6 (TSG-6) has a central role in the anti-inflammatory effects of MSCs. However, the mechanisms by which MSCs secrete TSG-6 and exert anti-inflammatory effects are not fully clarified. Here, we investigated these mechanisms using TSG-6-overexpressing MSCs (TSG-6 MSCs) with an adeno-associated virus. Extracellular vesicles (EVs) were isolated from MSC culture supernatants by ultracentrifugation. MSCs were injected through the abdominal aorta into rats with ischemia-reperfusion injury (IRI) to evaluate their anti-inflammatory and anti-fibrotic effects. Additionally, we explored natural compounds that increased TSG-6 expression in MSCs. Most TSG-6 was immediately secreted in EVs and was not stored intracellularly. Administration of TSG-6 MSCs strongly suppressed renal fibrosis and inflammation in IRI rats. Although EVs and conditioned medium from TSG-6 MSCs (TSG-6 MSC-CM) strongly promoted polarization of M2 macrophages, TSG-6 MSC-CM after EV depletion promoted it only slightly. Moreover, TSG-6 MSC-CM enhanced regulatory T-cell induction. MSCs treated with indole-3-carbinol had enhanced TSG-6 expression and markedly suppressed IRI-induced renal fibrosis. Taken together, TSG-6 is secreted in EVs from MSCs and exerts potent anti-inflammatory effects by promoting M2 macrophage polarization and regulatory T-cell induction. Administration of MSCs with enhanced TSG-6 secretion is a promising therapeutic strategy to impede AKI to CKD progression.","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":"143958680","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

Stem cells and female reproduction: endometrial physiology, disease and therapy. 干细胞与女性生殖：子宫内膜生理学、疾病和治疗。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-15 DOI: 10.1093/stmcls/sxaf016

E Cansu Cevik, Ramanaiah Mamillapalli, Hugh S Taylor

{"title":"Stem cells and female reproduction: endometrial physiology, disease and therapy.","authors":"E Cansu Cevik, Ramanaiah Mamillapalli, Hugh S Taylor","doi":"10.1093/stmcls/sxaf016","DOIUrl":"10.1093/stmcls/sxaf016","url":null,"abstract":"The human endometrium, a dynamic tissue that undergoes cyclical shedding, repair, regeneration, and remodeling, relies on progenitor stem cells for replenishment. Bone marrow-derived mesenchymal stem cells (BM-MSCs) also may play a crucial role in the physiological process of endometrial regeneration, augmenting endometrial repair, supporting pregnancy, and thereby making a major contribution to reproduction. Notably, defective or inappropriate recruitment and engraftment of stem cells are implicated in various reproductive diseases, including endometriosis, highlighting the potential therapeutic avenues offered by stem cell-targeted interventions. Endometrial progenitor cells have shown promise in improving pregnancy outcomes and addressing infertility issues. Furthermore, BM-MSCs demonstrate the potential to reverse pathologies, including Asherman's syndrome and thin endometrium, offering novel approaches to treating infertility, implantation failure, and recurrent pregnancy loss. Mobilization of endogenous stem cells to areas of pathology through chemoattractants also presents a promising strategy for targeted therapy. Finally, endometrium-derived mesenchymal stem cells, characterized by their multipotent nature and ease of collection through minimally invasive techniques, hold promise in a wide range of reproductive and non-reproductive pathologies, including diabetes, kidney disease, Parkinson's disease, or cardiac disorders. As the best of our knowledge of stem cell biology continues to grow, the incorporation of stem cell-based therapies into clinical practice presents significant potential to transform reproductive medicine and enhance patient outcomes.","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":"143962250","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