STEM CELLS最新文献_第6页

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

Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing. CD146+NESTIN+ HUMSCs 的细胞增殖和免疫调节优势：单细胞 RNA 测序的启示。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-21 DOI: 10.1093/stmcls/sxae063

Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma

{"title":"Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing.","authors":"Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma","doi":"10.1093/stmcls/sxae063","DOIUrl":"https://doi.org/10.1093/stmcls/sxae063","url":null,"abstract":"The heterogeneity of stem cells is a significant factor inhibiting their clinical application, as different cell subpopulations may exhibit substantial differences in biological functions. We performed single-cell sequencing on HUMSCs from three donors of different gestational ages (22 + 5 weeks, 28 weeks, 39 weeks). We also compared the data with single-cell sequencing data from BMSCs from two public databases. The content of CD146+Nestin+ MSCs in preterm HUMSCs (22 + 5W: 30.2%, 28W: 25.8%) was higher than that in full-term HUMSCs (39W: 0.5%) and BMSCs (BMSC1: 0, BMSC2: 0.9%). Cell cycle analysis indicated a higher proportion of cells in the proliferative G2M phase in CD146+Nestin+ MSCs (40.8%) compared to CD146+Nestin- MSCs (20%) and CD146-Nestin- MSCs (12.5%). Degree of differentiation assessment suggested that CD146+Nestin+ MSCs exhibited lower differentiation than other cell subpopulations. Differential gene analysis revealed that CD146+Nestin+ MSCs overexpressed immune regulation-related factors. GO and KEGG enrichment analysis of modules identified by WGCNA suggested enrichment in pathways related to cellular immune regulation, antimicrobial activity, and proliferation. Immune-related gene analysis indicated that CD146+Nestin+ MSCs exhibited expression of multiple immune-related genes associated with \"Antimicrobials,\" \"Cytokines,\" and \"Cytokine Receptors.\" Gene regulatory network analysis revealed high expression of immune-related regulators RELB, GAPB1, and EHF in CD146+Nestin+ MSCs.Our study provides a single-cell atlas of preterm HUMSCs, demonstrating the expression of CD146+Nestin+ MSCs across different tissues and confirming their advantages in cellular proliferation, antimicrobial activity, immune regulation, and low differentiation at the RNA level. This contributes valuable insights for the clinical application of HUMSCs.","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":"142454402","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

Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway. 整合素连接激酶通过 mTOR 信号通路控制牙髓干细胞衰老

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae047

Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou

{"title":"Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway.","authors":"Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou","doi":"10.1093/stmcls/sxae047","DOIUrl":"10.1093/stmcls/sxae047","url":null,"abstract":"Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affects the dental stromal tissue homeostasis and impairs the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated β-galactosidase (SA-β-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mammalian target of rapamycin (mTOR) signaling pathway (ILK, MAPK3, mTOR, STAT1, and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-β-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"861-873"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015888","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

TMEM16A regulates satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity. TMEM16A 通过确保适度的 Caspase 3 活性来调节卫星细胞介导的骨骼肌再生。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae048

Zhiyuan Sun, Xinqi Shan, Chun'e Fan, Lutao Liu, Shuai Li, Jiahui Wang, Na Zhou, Minsheng Zhu, Huaqun Chen

{"title":"TMEM16A regulates satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.","authors":"Zhiyuan Sun, Xinqi Shan, Chun'e Fan, Lutao Liu, Shuai Li, Jiahui Wang, Na Zhou, Minsheng Zhu, Huaqun Chen","doi":"10.1093/stmcls/sxae048","DOIUrl":"10.1093/stmcls/sxae048","url":null,"abstract":"It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a-/- SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a-/- SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"902-913"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887741","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

Metabolic conditioning enhances human bmMSC therapy of doxorubicin-induced heart failure. 新陈代谢调节增强了人类 bmMSC 对多柔比星诱发的心力衰竭的治疗效果。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae050

Virginie Jacques, Sabrina Benaouadi, Jean-Gerard Descamps, Nicolas Reina, Nicolas Espagnolle, Dimitri Marsal, Yannis Sainte-Marie, Alexandre Boudet, Carla Pinto, Thomas Farge, Frédérique Savagner

{"title":"Metabolic conditioning enhances human bmMSC therapy of doxorubicin-induced heart failure.","authors":"Virginie Jacques, Sabrina Benaouadi, Jean-Gerard Descamps, Nicolas Reina, Nicolas Espagnolle, Dimitri Marsal, Yannis Sainte-Marie, Alexandre Boudet, Carla Pinto, Thomas Farge, Frédérique Savagner","doi":"10.1093/stmcls/sxae050","DOIUrl":"10.1093/stmcls/sxae050","url":null,"abstract":"The therapeutic potential of bone marrow mesenchymal stromal cells (bmMSCs) to address heart failure needs improvement for better engraftment and survival. This study explores the role of metabolic sorting for human bmMSCs in coculture in vitro and on doxorubicin-induced heart failure mice models. Using functional, epigenetic, and gene expression approaches on cells sorted for mitochondrial membrane potential in terms of their metabolic status, we demonstrated that bmMSCs selected for their glycolytic metabolism presented proliferative advantage and resistance to oxidative stress thereby favoring cell engraftment. Therapeutic use of glycolytic bmMSCs rescued left ventricular ejection fraction and decreased fibrosis in mice models of acute heart failure. Metabolic changes were also related to epigenetic histone modifications such as lysine methylation. By targeting LSD1 (lysine-specific demethylase 1) as a conditioning agent to enhance the metabolic profile of bmMSCs, we deciphered the interplay between glycolysis and bmMSC functionality. Our study elucidates novel strategies for optimizing bmMSC-based treatments for heart failure, highlighting the metabolic properties of bmMSCs as a promising target for more effective cardiovascular regenerative therapies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"874-888"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915670","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

Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation. 沉默骨髓窦中的内黏蛋白可改善移植过程中造血干细胞和祖细胞的归巢。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae046

Yue Li, Miao Ren, Hu Li, Zuo Zhang, Ke Yuan, Yujin Huang, Shengnan Yuan, Wen Ju, Yuan He, Kailin Xu, Lingyu Zeng

{"title":"Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation.","authors":"Yue Li, Miao Ren, Hu Li, Zuo Zhang, Ke Yuan, Yujin Huang, Shengnan Yuan, Wen Ju, Yuan He, Kailin Xu, Lingyu Zeng","doi":"10.1093/stmcls/sxae046","DOIUrl":"10.1093/stmcls/sxae046","url":null,"abstract":"Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short-interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"889-901"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589138","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