STEM CELLS最新文献_第2页

Comment on "Changes in iPSC-Astrocyte Morphology Reflect Alzheimer's Disease Patient Clinical Markers". “ipsc -星形胶质细胞形态变化反映阿尔茨海默病患者临床标志物”评论

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-13 DOI: 10.1093/stmcls/sxaf030

Leepy Paudel

引用次数: 0

Cerulenin Partially Corrects the Disrupted Developmental Transcriptomic Signature in Huntington's Disease Striatal Medium Spiny Neurons. 蓝绿蛋白部分纠正亨廷顿氏病纹状体中棘神经元发育转录组特征的中断。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-08 DOI: 10.1093/stmcls/sxaf029

Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov, Michelle E Ehrlich, Lisa M Ellerby

{"title":"Cerulenin Partially Corrects the Disrupted Developmental Transcriptomic Signature in Huntington's Disease Striatal Medium Spiny Neurons.","authors":"Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov, Michelle E Ehrlich, Lisa M Ellerby","doi":"10.1093/stmcls/sxaf029","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf029","url":null,"abstract":"Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene, resulting in a mutant HTT (mHTT) protein. Although mHTT is expressed in all tissues, it significantly affects medium spiny neurons (MSNs) in the striatum, resulting in their loss and the subsequent motor function impairment in HD. While HD symptoms typically emerge in midlife, disrupted MSN neurodevelopment is important. To explore the effects of mHTT on MSN development, we differentiated HD-induced pluripotent stem cells (iPSC) and isogenic controls into neuronal stem cells, and then generated a developing MSN population encompassing early, intermediate progenitors, and nascent MSNs. Single-cell RNA sequencing revealed that the developmental trajectory of MSNs in our model closely emulated the trajectory of human fetal striatal neurons. However, in the HD MSN cultures, several crucial genes required for proper MSN maturation were downregulated, including members of the DLX family of transcription factors. Our analysis also uncovered a progressive dysregulation of multiple HD-related pathways as MSNs developed, including the NRF2-mediated oxidative stress response and mitogen-activated protein kinase signaling. Using the transcriptional profile of developing HD MSNs, we searched the L1000 dataset for small molecules that induce the opposite gene expression pattern. We pinpointed numerous small molecules with known benefits in HD models and previously untested novel molecules. A top candidate, Cerulenin, partially restored the DARPP-32 levels and electrical activity in HD MSNs, and also modulated genes involved in multiple HD-related pathways.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961537","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

DNA hydroxymethylases Tet1 and Tet2 regulate bone aging and BMSC metabolism through the IGF-1/ mTOR signalling axis. DNA羟甲基化酶Tet1和Tet2通过IGF-1/ mTOR信号轴调节骨老化和BMSC代谢。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-06 DOI: 10.1093/stmcls/sxaf026

Nicholas Smith, Dimitrios Cakouros, Feargal J Ryan, David J Lynn, Sharon Paton, Agnieszka Arthur, Stan Gronthos

{"title":"DNA hydroxymethylases Tet1 and Tet2 regulate bone aging and BMSC metabolism through the IGF-1/ mTOR signalling axis.","authors":"Nicholas Smith, Dimitrios Cakouros, Feargal J Ryan, David J Lynn, Sharon Paton, Agnieszka Arthur, Stan Gronthos","doi":"10.1093/stmcls/sxaf026","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf026","url":null,"abstract":"The Ten-Eleven Translocases (Tet) family of DNA hydroxymethylases have recently been implicated in bone development, with Tet1 and Tet2 mediating Bone Marrow Stromal Cell (BMSC) growth and osteogenic differentiation. The present study investigated the effects of Tet1 and Tet2 deregulation on bone development and age-related bone loss, with respect to BMSC function. Histomorphometric and micro-CT analysis of skeletal parameters found significant reductions to trabecular structure and volume as well as reduced osteoblast numbers within the bone of Prx-1:Cre driven Tet1 and Tet2 double knockout (TetDKO) mice at skeletal maturity. Moreover, these effects were exacerbated with age, particularly in male mice. In vitro studies found a significant reduction in TetDKO BMSC osteogenic potential and a shift towards adipogenesis, as well as changes to DNA repair, proliferation and senescence properties. RNA sequencing of BMSC derived from TetDKO male mice uncovered several differentially expressed genes, and an array of significantly enriched gene set pathways. Notably Pappa2, involved in regulation of IGF-1 signalling, was significantly differentially regulated, leading to reduction in IGF-1 bioavailability and signalling in BMSC and differentiated osteoblasts. Furthermore, changes in mTOR activity in TetDKO animals indicated altered metabolic activity, differentiation and proliferation capabilities of TetDKO BMSC. These findings indicate that Tet1 and 2 regulate the IGF-1 regulatory element, Pappa2, where deregulation of Tet1 and Tet2 in BMSC can disrupt this pathway leading to enhanced bone loss and premature aging. Targeting of these novel regulatory pathways may offer new therapeutic approaches for treatment of age-related bone loss.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961839","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

Fibroblast activation protein-α interacts with CXCL12 to inactivate canonical Wnt signaling and regulate osteoblast differentiation. 成纤维细胞活化蛋白-α与CXCL12相互作用使典型Wnt信号失活并调节成骨细胞分化。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-06 DOI: 10.1093/stmcls/sxaf027

Yuan Dong, Xingli Hu, Wei Liu, Yinglong Hao, Jie Zhou, Xiaoxia Li, Baoli Wang

{"title":"Fibroblast activation protein-α interacts with CXCL12 to inactivate canonical Wnt signaling and regulate osteoblast differentiation.","authors":"Yuan Dong, Xingli Hu, Wei Liu, Yinglong Hao, Jie Zhou, Xiaoxia Li, Baoli Wang","doi":"10.1093/stmcls/sxaf027","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf027","url":null,"abstract":"Fibroblast activation protein-α (FAP) has been identified as an osteogenic suppressor and a potential drug target to treat osteoporosis. However, the direct role of FAP in osteoblast differentiation and the mechanism by which FAP works remains to be explored. In the current study we showed that FAP expression increased significantly during osteogenic and adipogenic differentiation of mesenchymal progenitor cells. Functional experiments revealed that FAP suppressed osteoblast differentiation and forced adipocyte formation from mesenchymal progenitor cells. Mechanistic exploration showed that FAP reduced the protein level of C-X-C motif chemokine ligand 12 (CXCL12) through directly degrading the latter. Consistently, the point mutation of the catalytic site rendered FAP fail to reduce CXCL12 protein level and fail to impact osteoblast and adipocyte differentiation. While CXCL12 activated canonical Wnt pathway, FAP inactivated canonical Wnt signaling to regulate differentiation of osteoblasts and adipocytes. CXCL12 was able to promote osteoblast differentiation while suppressing adipocyte differentiation, and attenuated the dysregulation of the differentiation tendencies induced by FAP. Taken as a whole, our study has demonstrated that FAP directly cleaves CXCL12 to inactivate canonical Wnt signaling, and therefore plays a direct role in regulating osteogenic and adipogenic differentiation of mesenchymal progenitor cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958868","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

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 : 2025-05-04 DOI: 10.1093/stmcls/sxaf025

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

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 : 2025-04-29 DOI: 10.1093/stmcls/sxaf021

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

引用次数: 0

E3 ligase Trim63 promotes the chondrogenic differentiation of mesenchymal stem cells by catalyzing K27-linked cysteine ubiquitination of Myh11. E3连接酶Trim63通过催化K27-linked半胱氨酸泛素化Myh11促进间充质干细胞的软骨分化。

IF 4 2区医学

STEM CELLS Pub Date : 2025-04-29 DOI: 10.1093/stmcls/sxaf017

Shanyu Ye, Yanqing Wang, Ziwei Luo, Aijun Liu, Xican Li, Jiasong Guo, Wei Zhao, Dongfeng Chen, Lin Yang, Helu Liu

{"title":"E3 ligase Trim63 promotes the chondrogenic differentiation of mesenchymal stem cells by catalyzing K27-linked cysteine ubiquitination of Myh11.","authors":"Shanyu Ye, Yanqing Wang, Ziwei Luo, Aijun Liu, Xican Li, Jiasong Guo, Wei Zhao, Dongfeng Chen, Lin Yang, Helu Liu","doi":"10.1093/stmcls/sxaf017","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf017","url":null,"abstract":"Mesenchymal stem cells (MSCs) are multipotent stem cells that have a chondrogenic differentiation capacity. However, the molecular mechanism underlying the chondrogenic differentiation of MSCs has not been fully elucidated, which hinders further development of MSC-based cell therapies for cartilage repair in the clinic. Here, we showed that the E3 ubiquitin ligase Trim63 positively regulates the chondrogenic differentiation of MSCs by catalyzing K27-linked cysteine ubiquitination of Myh11. Trim63 directly interacts with Myh11 and catalyzes K27-linked ubiquitination of cys382. Mutation of cys382 diminishes Trim63-catalyzed K27-linked ubiquitination and chondrogenic differentiation of MSCs. A deficiency in Trim63 significantly impairs the chondrogenic differentiation of MSCs. Trim63 enhances the repair of articular cartilage defects in vivo. Taken together, the results of our study demonstrated that Trim63 promotes the chondrogenic differentiation of MSCs by catalyzing K27-linked cysteine ubiquitination of Myh11, which provides an alternative therapeutic target for cartilage regeneration and repair.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956961","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 : 2025-04-22 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":"https://doi.org/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":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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. 自身免疫和GVHD同种免疫中ipsc衍生的免疫调节非淋巴细胞后代。

IF 4 2区医学

STEM CELLS Pub Date : 2025-04-22 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":"10.1093/stmcls/sxaf011","url":null,"abstract":"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.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-22","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

Raman spectroscopies for cancer research and clinical applications: a focus on cancer stem cells. 癌症研究和临床应用的拉曼光谱：聚焦于癌症干细胞。

IF 4 2区医学

STEM CELLS Pub Date : 2025-04-22 DOI: 10.1093/stmcls/sxae084

Francesca Pagliari, Luca Tirinato, Enzo Di Fabrizio

{"title":"Raman spectroscopies for cancer research and clinical applications: a focus on cancer stem cells.","authors":"Francesca Pagliari, Luca Tirinato, Enzo Di Fabrizio","doi":"10.1093/stmcls/sxae084","DOIUrl":"10.1093/stmcls/sxae084","url":null,"abstract":"Over the last 2 decades, research has increasingly focused on cancer stem cells (CSCs), considered responsible for tumor formation, resistance to therapies, and relapse. The traditional \"static\" CSC model used to describe tumor heterogeneity has been challenged by the evidence of CSC dynamic nature and plasticity. A comprehensive understanding of the mechanisms underlying this plasticity, and the capacity to unambiguously identify cancer markers to precisely target CSCs are crucial aspects for advancing cancer research and introducing more effective treatment strategies. In this context, Raman spectroscopy (RS) and specific Raman schemes, including CARS, SRS, SERS, have emerged as innovative tools for molecular analyses both in vitro and in vivo. In fact, these techniques have demonstrated considerable potential in the field of cancer detection, as well as in intraoperative settings, thanks to their label-free nature and minimal invasiveness. However, the RS integration in pre-clinical and clinical applications, particularly in the CSC field, remains limited. This review provides a concise overview of the historical development of RS and its advantages. Then, after introducing the CSC features and the challenges in targeting them with traditional methods, we review and discuss the current literature about the application of RS for revealing and characterizing CSCs and their inherent plasticity, including a brief paragraph about the integration of artificial intelligence with RS. By providing the possibility to better characterize the cellular diversity in their microenvironment, RS could revolutionize current diagnostic and therapeutic approaches, enabling early identification of CSCs and facilitating the development of personalized treatment strategies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412637","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