STEM CELLS最新文献_第4页

Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia. 间充质基质细胞移植可改善骨骼肌缺血中的纤维化和微RNA失调。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae058

Clara Sanz-Nogués, Alan J Keane, Michael Creane, Sean O Hynes, Xizhe Chen, Caomhán J Lyons, Emma Horan, Stephen J Elliman, Katarzyna Goljanek-Whysall, Timothy O'Brien

{"title":"Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia.","authors":"Clara Sanz-Nogués, Alan J Keane, Michael Creane, Sean O Hynes, Xizhe Chen, Caomhán J Lyons, Emma Horan, Stephen J Elliman, Katarzyna Goljanek-Whysall, Timothy O'Brien","doi":"10.1093/stmcls/sxae058","DOIUrl":"10.1093/stmcls/sxae058","url":null,"abstract":"Peripheral arterial disease (PAD) is associated with lower-extremity muscle wasting. Hallmark features of PAD-associated skeletal muscle pathology include loss of skeletal muscle mass, reduced strength and physical performance, increased inflammation, fibrosis, and adipocyte infiltration. At the molecular level, skeletal muscle ischemia has also been associated with gene and microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have been shown to enhance muscle regeneration and improve muscle function in various skeletal muscle injuries. This study aimed to evaluate the effects of intramuscularly delivered human umbilical cord-derived MSCs (hUC-MSCs) on skeletal muscle ischemia. Herein, we report an hUC-MSC-mediated amelioration of ischemia-induced skeletal muscle atrophy and function via enhancement of myofiber regeneration, reduction of tissue inflammation, adipocyte accumulation, and tissue fibrosis. These changes were observed in the absence of cell-mediated enhancement of blood flow recovery as measured by laser Doppler imaging. Furthermore, reduced tissue fibrosis in the hUC-MSC-treated group was associated with upregulation of miR-1, miR-133a, and miR-29b and downregulation of targeted pro-fibrotic genes such as Col1a1 and Fn1. Our results support the use of hUC-MSCs as a novel approach to reduce fibrosis and promote skeletal muscle regeneration after ischemic injury in patients with PAD.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"976-991"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277716","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

The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent. 糖皮质激素受体诱导的人类红细胞增殖反应依赖于 BCL11A。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae049

Maria Mazzarini, Jennifer Cherone, Truong Nguyen, Fabrizio Martelli, Lilian Varricchio, Alister P W Funnell, Thalia Papayannopoulou, Anna Rita Migliaccio

{"title":"The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent.","authors":"Maria Mazzarini, Jennifer Cherone, Truong Nguyen, Fabrizio Martelli, Lilian Varricchio, Alister P W Funnell, Thalia Papayannopoulou, Anna Rita Migliaccio","doi":"10.1093/stmcls/sxae049","DOIUrl":"10.1093/stmcls/sxae049","url":null,"abstract":"Prior evidence indicates that the erythroid cellular response to glucocorticoids (GC) has developmental specificity, namely, that developmentally more advanced cells that are undergoing or have undergone fetal to adult globin switching are more responsive to GC-induced expansion. To investigate the molecular underpinnings of this, we focused on the major developmental globin regulator BCL11A. We compared: (1) levels of expression and nuclear content of BCL11A in adult erythroid cells upon GC stimulation; (2) response to GC of CD34+ cells from patients with BCL11A microdeletions and reduced BCL11A expression, and; (3) response to GC of 2 cellular models (HUDEP-2 and adult CD34+ cells) before and after reduction of BCL11A expression by shRNA. We observed that: (1) GC-expanded erythroid cells from a large cohort of blood donors displayed amplified expression and nuclear accumulation of BCL11A; (2) CD34 + cells from BCL11A microdeletion patients generated fewer erythroid cells when cultured with GC compared to their parents, while the erythroid expansion of the patients was similar to that of their parents in cultures without GC, and; (3) adult CD34+ cells and HUDEP-2 cells with shRNA-depleted expression of BCL11A exhibit reduced expansion in response to GC. In addition, RNA-seq profiling of shRNA-BCL11A CD34+ cells cultured with and without GC was similar (very few differentially expressed genes), while GC-specific responses (differential expression of GILZ and of numerous additional genes) were observed only in control cells with unperturbed BCL11A expression. These data indicate that BCL11A is an important participant in certain aspects of the stress pathway sustained by GC.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1006-1022"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896299","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

A p21 reporter iPSC line for evaluating CRISPR-Cas9 and vector-induced stress responses. 用于评估 CRISPR-Cas9 和载体诱导的应激反应的 p21 报告 iPSC 系。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae056

Yi-Dan Sun, Guo-Hua Li, Feng Zhang, Tao Cheng, Jian-Ping Zhang, Xiao-Bing Zhang

{"title":"A p21 reporter iPSC line for evaluating CRISPR-Cas9 and vector-induced stress responses.","authors":"Yi-Dan Sun, Guo-Hua Li, Feng Zhang, Tao Cheng, Jian-Ping Zhang, Xiao-Bing Zhang","doi":"10.1093/stmcls/sxae056","DOIUrl":"10.1093/stmcls/sxae056","url":null,"abstract":"CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors. Highlights Established a p21-mNeonGreen reporter iPSC line to track activation of the TP53-p21 pathway. Found a direct correlation between p21-mNeonGreen expression and indel frequencies, aiding in gRNA screening. Showed that LVs are preferable over AAVs for certain cells due to lower p21 activation, with viral promoter choice impacting p21 response.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"992-1005"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277715","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

Correction to: High-Mobility Group At-Hook 1 Mediates the Role of Nuclear Factor I/X in Osteogenic Differentiation Through Activating Canonical Wnt Signaling. Correction to：高流动性基团 At-Hook 1 通过激活经典 Wnt 信号在成骨分化过程中调节核因子 I/X 的作用

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae061

引用次数: 0

Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration. 从小鼠胚胎干细胞中衍生出用于牙齿再生的牙上皮样细胞。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae052

Hong Hu, Yifan Zhao, Ce Shan, Huancheng Fu, Jinglei Cai, Zhonghan Li

{"title":"Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration.","authors":"Hong Hu, Yifan Zhao, Ce Shan, Huancheng Fu, Jinglei Cai, Zhonghan Li","doi":"10.1093/stmcls/sxae052","DOIUrl":"10.1093/stmcls/sxae052","url":null,"abstract":"Teeth are comprised of epithelial and mesenchymal cells, and regenerative teeth rely on the regeneration of both cell types. Transcription factors play a pivotal role in cell fate determination. In this study, we establish fluorescence models based on transcription factors to monitor and analyze dental epithelial cells. Using Pitx2-P2A-copGFP mice, we observe that Pitx2+ epithelial cells, when combined with E14.5 dental mesenchymal cells, are sufficient for the reconstitution of teeth. Induced-Pitx2+ cells, directly isolated from the embryoid body that employs the Pitx2-GFP embryonic stem cell line, exhibit the capacity to differentiate into ameloblasts and develop into teeth when combined with dental mesenchymal cells. The regenerated teeth exhibit a complete structure, including dental pulp, dentin, enamel, and periodontal ligaments. Subsequent exploration via RNA-seq reveals that induced-Pitx2+ cells exhibit enrichment in genes associated with FGF receptors and WNT ligands compared with induced-Pitx2- cells. Our results indicate that both primary Pitx2+ and induced Pitx2+ cells possess the capability to differentiate into enamel-secreting ameloblasts and grow into teeth when combined with dental mesenchymal cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"945-956"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034678","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

The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review. 系统生物学和人工智能在干细胞研究和治疗开发中的全球演变和影响：范围综述》。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae054

Thayna Silva-Sousa, Júlia Nakanishi Usuda, Nada Al-Arawe, Francisca Frias, Irene Hinterseher, Rusan Catar, Christian Luecht, Katarina Riesner, Alexander Hackel, Lena F Schimke, Haroldo Dutra Dias, Igor Salerno Filgueiras, Helder I Nakaya, Niels Olsen Saraiva Camara, Stefan Fischer, Gabriela Riemekasten, Olle Ringdén, Olaf Penack, Tobias Winkler, Georg Duda, Dennyson Leandro M Fonseca, Otávio Cabral-Marques, Guido Moll

{"title":"The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review.","authors":"Thayna Silva-Sousa, Júlia Nakanishi Usuda, Nada Al-Arawe, Francisca Frias, Irene Hinterseher, Rusan Catar, Christian Luecht, Katarina Riesner, Alexander Hackel, Lena F Schimke, Haroldo Dutra Dias, Igor Salerno Filgueiras, Helder I Nakaya, Niels Olsen Saraiva Camara, Stefan Fischer, Gabriela Riemekasten, Olle Ringdén, Olaf Penack, Tobias Winkler, Georg Duda, Dennyson Leandro M Fonseca, Otávio Cabral-Marques, Guido Moll","doi":"10.1093/stmcls/sxae054","DOIUrl":"10.1093/stmcls/sxae054","url":null,"abstract":"Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024. We identified an 8 to 10-fold increase in research output related to all 3 search terms between 2000 and 2021, with a 10-fold increase in AI-related production since 2010. Use of SysBio and AI still predominates in preclinical basic research with increasing use in clinically oriented translational medicine since 2010. SysBio- and AI-related research was found all over the globe, with SysBio output led by the (US, n = 1487), (UK, n = 1094), Germany (n = 355), The Netherlands (n = 339), Russia (n = 215), and France (n = 149), while for AI-related research the US (n = 853) and UK (n = 258) take a strong lead, followed by Switzerland (n = 69), The Netherlands (n = 37), and Germany (n = 19). The US and UK are most active in SCs publications related to AI/ML and AI/DL. The prominent use of SysBio in ESC research was recently overtaken by prominent use of AI in iPSC and MSC research. This study reveals the global evolution and growing intersection among AI, SysBio, and SC research over the past 2 decades, with substantial growth in all 3 fields and exponential increases in AI-related research in the past decade.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"929-944"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124308","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

A de novo Missense Mutation in PPP2R5D Alters Dopamine Pathways and Morphology of iPSC-derived Midbrain Neurons. PPP2R5D中的一个新发缺义突变改变了多巴胺通路和iPSC衍生中脑神经元的形态。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-26 DOI: 10.1093/stmcls/sxae068

Jasmine L Carter, Julian A N M Halmai, Jennifer J Waldo, Paula A Vij, Maribel Anguiano, Isaac J Villegas, Yu Xin Du, Jan Nolta, Kyle D Fink

{"title":"A de novo Missense Mutation in PPP2R5D Alters Dopamine Pathways and Morphology of iPSC-derived Midbrain Neurons.","authors":"Jasmine L Carter, Julian A N M Halmai, Jennifer J Waldo, Paula A Vij, Maribel Anguiano, Isaac J Villegas, Yu Xin Du, Jan Nolta, Kyle D Fink","doi":"10.1093/stmcls/sxae068","DOIUrl":"https://doi.org/10.1093/stmcls/sxae068","url":null,"abstract":"Induced pluripotent stem cell (iPSC) models of neurodevelopmental disorders (NDDs) have promoted an understanding of commonalities and differences within or across patient populations by revealing the underlying molecular and cellular mechanisms contributing to disease pathology. Here, we focus on developing a human model for PPP2R5D-related NDD, called Jordan syndrome, which has been linked to Early-Onset Parkinson's Disease (EOPD). Here we sought to understand the underlying molecular and cellular phenotypes across multiple cell states and neuronal subtypes in order to gain insight into Jordan syndrome pathology. Our work revealed that iPSC-derived midbrain neurons from Jordan syndrome patients display significant differences in dopamine-associated pathways and neuronal architecture. We then evaluated a CRISPR-based approach for editing heterozygous dominant G-to-A mutations at the transcript level in patient-derived neural stem cells. Our findings show site-directed RNA editing is influenced by sgRNA length and cell type. These studies support the potential for a CRISPR RNA editor system to selectively edit mutant transcripts harboring G-to-A mutations in neural stem cells while providing an alternative editing technology for those suffering from NDDs.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491797","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

High-throughput solutions in tumor organoids: From culture to drug screening. 肿瘤器官组织的高通量解决方案：从培养到药物筛选。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-26 DOI: 10.1093/stmcls/sxae070

Jianing Zuo, Yanhua Fang, Ruoyu Wang, Shan Shan Liang

引用次数: 0

USP13 Overexpression in BMSCs Enhances Anti-Apoptotic Ability and Guards Against Methylprednisolone-Induced Osteonecrosis in Rats. USP13 在 BMSCs 中的过表达可增强抗凋亡能力，防止甲泼尼龙诱导的大鼠骨坏死。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-26 DOI: 10.1093/stmcls/sxae069

Yixin Jiang, Xiaoli Fan, Yaling Yu, Hongfan Ge, Chengyin Liu, Yanyan Zhang, Lingyun Yu, Wen Yin, Zhenlei Zhou

引用次数: 0

RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells. RSPO/LGR 信号调节成体海马神经干细胞的增殖。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-21 DOI: 10.1093/stmcls/sxae065

Daniela Valenzuela-Bezanilla, Muriel D Mardones, Maximiliano Galassi, Sebastian B Arredondo, Sebastian H Santibanez, Stephanie Gutierrez-Jimenez, Nicolás Merino-Véliz, Fernando J Bustos, Lorena Varela-Nallar

{"title":"RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells.","authors":"Daniela Valenzuela-Bezanilla, Muriel D Mardones, Maximiliano Galassi, Sebastian B Arredondo, Sebastian H Santibanez, Stephanie Gutierrez-Jimenez, Nicolás Merino-Véliz, Fernando J Bustos, Lorena Varela-Nallar","doi":"10.1093/stmcls/sxae065","DOIUrl":"https://doi.org/10.1093/stmcls/sxae065","url":null,"abstract":"In the dentate gyrus of the adult hippocampus, neurogenesis from neural stem cells (NSCs) is regulated by Wnt signals from the local microenvironment. The Wnt/β-catenin pathway is active in NSCs, where it regulates proliferation and fate commitment, and subsequently its activity is strongly attenuated. The mechanisms controlling Wnt activity are poorly understood. In stem cells from adult peripheral tissues, secreted R-spondin proteins (RSPO1-4) interact with LGR4-6 receptors and control Wnt signaling strength. Here, we found that RSPO1-3 and LGR4-6 are expressed in the adult dentate gyrus and in cultured NSCs isolated from the adult mouse hippocampus. LGR4-5 expression decreased in cultured NSCs upon differentiation, concomitantly with the reported decrease in Wnt activity. Treatment with RSPO1-3 increased NSC proliferation and the expression of Cyclin D1, but did not induce the expression of Axin2 or RNF43, two well-described Wnt target genes. However, RSPOs enhanced the effect of Wnt3a on Axin2 and RNF43 expression, as well as on Wnt/β-catenin reporter activity, indicating that they can potentiate Wnt activity in NSCs. Moreover, RSPO1-3 were found to be expressed by cultured dentate gyrus astrocytes, a crucial component of the neurogenic niche. In co-culture experiments, the astrocyte-induced proliferation of NSCs was prevented by RSPO2 knockdown in astrocytes and LGR5 knockdown in hippocampal NSCs. Additionally, RSPO2 knockdown in the adult mouse dentate gyrus reduced proliferation of neural stem and progenitor cells in vivo. Altogether, our results indicate that RSPO/LGR signaling is present in the dentate gyrus and plays a crucial role in regulating neural precursor cell proliferation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454404","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