STEM CELLS最新文献_第10页

LSD1 Regulates Neurogenesis in Human Neural Stem Cells Through the Repression of Human-Enriched Extracellular Matrix and Cell Adhesion Genes. LSD1 通过抑制人类丰富细胞外基质和细胞粘附基因调控人类神经干细胞的神经发生

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad088

Asha S Channakkar, Leora D'Souza, Aparajita Kumar, Kishan Kalia, Srilekha Prabhu, Kruttika Phalnikar, Puli Chandramouli Reddy, Bhavana Muralidharan

{"title":"LSD1 Regulates Neurogenesis in Human Neural Stem Cells Through the Repression of Human-Enriched Extracellular Matrix and Cell Adhesion Genes.","authors":"Asha S Channakkar, Leora D'Souza, Aparajita Kumar, Kishan Kalia, Srilekha Prabhu, Kruttika Phalnikar, Puli Chandramouli Reddy, Bhavana Muralidharan","doi":"10.1093/stmcls/sxad088","DOIUrl":"10.1093/stmcls/sxad088","url":null,"abstract":"Neurogenesis begins with neural stem cells undergoing symmetric proliferative divisions to expand and then switching to asymmetric differentiative divisions to generate neurons in the developing brain. Chromatin regulation plays a critical role in this switch. Histone lysine-specific demethylase LSD1 demethylates H3K4me1/2 and H3K9me1/2 but the mechanisms of its global regulatory functions in human neuronal development remain unclear. We performed genome-wide ChIP-seq of LSD1 occupancy, RNA-seq, and Histone ChIP-seq upon LSD1 inhibition to identify its repressive role in human neural stem cells. Novel downstream effectors of LSD1 were identified, including the Notch signaling pathway genes and human-neural progenitor-enriched extracellular matrix (ECM) pathway/cell adhesion genes, which were upregulated upon LSD1 inhibition. LSD1 inhibition led to decreased neurogenesis, and overexpression of downstream effectors mimicked this effect. Histone ChIP-seq analysis revealed that active and enhancer markers H3K4me2, H3K4me1, and H3K9me1 were upregulated upon LSD1 inhibition, while the repressive H3K9me2 mark remained mostly unchanged. Our work identifies the human-neural progenitor-enriched ECM pathway/cell adhesion genes and Notch signaling pathway genes as novel downstream effectors of LSD1, regulating neuronal differentiation in human neural stem cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"128-145"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139047855","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

Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions. 神经肽物质P可改变干细胞的命运，通过不对称干细胞分裂帮助伤口愈合并促进表皮分层。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-01 DOI: 10.1093/stmcls/sxae009

A Khalifa, T Xiao, B Abegaze, T Weisenberger, A Charruyer, Samia Sanad, Taher AbuElnasr, S W Kashem, M Fassett, R Ghadially

{"title":"Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions.","authors":"A Khalifa, T Xiao, B Abegaze, T Weisenberger, A Charruyer, Samia Sanad, Taher AbuElnasr, S W Kashem, M Fassett, R Ghadially","doi":"10.1093/stmcls/sxae009","DOIUrl":"10.1093/stmcls/sxae009","url":null,"abstract":"Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139670980","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

Single-Cell RNA Sequencing Technology Landscape in 2023. 2023年单细胞RNA测序技术展望。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad077

Hui-Qi Qu, Charlly Kao, Hakon Hakonarson

引用次数: 0

Critical Role of miR-130b-5p in Cardiomyocyte Proliferation and Cardiac Repair in Mice After Myocardial Infarction. miR-130b-5p在心肌梗死后小鼠心肌细胞增殖和心脏修复中的关键作用。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad080

Ke Feng, Yukang Wu, Jianguo Li, Qiaoyi Sun, Zihui Ye, Xuan Li, Xudong Guo, Jiuhong Kang

引用次数: 0

Bitter Taste Receptor Agonist Denatonium Inhibits Stemness Characteristics in Hematopoietic Stem/Progenitor Cells. 苦味受体激动剂Denatonium抑制造血干/祖细胞的Stemness特性。

IF 4 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad075

Valentina Pensato, Maria Antonella Laginestra, Paolo Falvo, Stefania Orecchioni, Giovanna Talarico, Elena De Marchi, Samantha Bruno, Sara Mongiorgi, Giulia Mitola, Francesco Bertolini, Elena Adinolfi, Michele Cavo, Antonio Curti, Valentina Salvestrini

{"title":"Bitter Taste Receptor Agonist Denatonium Inhibits Stemness Characteristics in Hematopoietic Stem/Progenitor Cells.","authors":"Valentina Pensato, Maria Antonella Laginestra, Paolo Falvo, Stefania Orecchioni, Giovanna Talarico, Elena De Marchi, Samantha Bruno, Sara Mongiorgi, Giulia Mitola, Francesco Bertolini, Elena Adinolfi, Michele Cavo, Antonio Curti, Valentina Salvestrini","doi":"10.1093/stmcls/sxad075","DOIUrl":"10.1093/stmcls/sxad075","url":null,"abstract":"Bone marrow microenvironmental stimuli profoundly impact hematopoietic stem cell fate and biology. As G protein-coupled receptors, the bitter taste receptors (TAS2Rs) are key in transmitting extracellular stimuli into an intracellular response, within the oral cavity but also in extraoral tissues. Their expression in the bone marrow (BM)-derived cells suggests their involvement in sensing the BM microenvironmental fluctuation. In the present study, we demonstrated that umbilical cord blood (UCB)-derived CD34+ cells express fully functional TAS2Rs along with the signal transduction cascade components and their activation by the prototypical agonist, denatonium benzoate, significantly modulated genes involved in stemness maintenance and regulation of cell trafficking. The activation of these specific pathways was confirmed in functional in vitro experiments. Denatonium exposure exerted an antiproliferative effect on UCB-derived CD34+ cells, mainly affecting the most undifferentiated progenitor frequency. It also reduced their clonogenicity and repopulating potential in vitro. In addition, the TAS2R signaling activation impaired the UCB-derived CD34+ cell trafficking, mainly reducing the migration toward the chemoattractant agent CXCL12 and modulating the expression of the adhesion molecules CD62L, CD49d, and CD29. In conclusion, our results in UCB-derived CD34+ cells expand the observation of TAS2R expression in the setting of BM-resident cells and shed light on the role of TAS2Rs in the extrinsic regulation of hematopoietic stem cell functions.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"42-54"},"PeriodicalIF":4.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10787278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101473","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

MSC-Derived Small Extracellular Vesicles Alleviate Diabetic Retinopathy by Delivering miR-22-3p to Inhibit NLRP3 Inflammasome Activation. MSC衍生的细胞外小泡通过递送miR-22-3p抑制NLRP3炎症小体激活来缓解糖尿病视网膜病变。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad078

Yueqin Chen, Genhong Yao, Jun Tong, Hairong Xie, Xinyu Zheng, Huayong Zhang, Zhenggao Xie

{"title":"MSC-Derived Small Extracellular Vesicles Alleviate Diabetic Retinopathy by Delivering miR-22-3p to Inhibit NLRP3 Inflammasome Activation.","authors":"Yueqin Chen, Genhong Yao, Jun Tong, Hairong Xie, Xinyu Zheng, Huayong Zhang, Zhenggao Xie","doi":"10.1093/stmcls/sxad078","DOIUrl":"10.1093/stmcls/sxad078","url":null,"abstract":"Purpose: This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism.Methods: In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism.Results: In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function. Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation. Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats. Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro. In vitro, compared with sEV, the anti-inflammation effect of sEVmiR-22-3p(-) on AGEs-induced microglia was compromised, as they gave a lower suppression of NLRP3 inflammasome activation and inflammatory cytokines. In addition, NLRP3 overexpression in microglia damped the anti-inflammatory effect of sEV.Conclusion: These results indicated that MSC-sEVs alleviated DR via delivering miR-22-3p to inhibit NLRP3 inflammasome activation. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"64-75"},"PeriodicalIF":5.2,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41230958","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

Mesenchymal Cells Retain the Specificity of Embryonal Origin During Osteogenic Differentiation. 间充质细胞在成骨分化过程中保持胚胎起源的特异性。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad081

Arseniy Lobov, Polina Kuchur, Aigul Khizhina, Anastasia Kotova, Andrei Ivashkin, Daria Kostina, Polina Klausen, Evgeniia Khokhlova, Egor Repkin, Kseniia Postnikova, Daria Perepletchikova, Evgeny Denisov, Tatiana Gerashchenko, Rashid Tikhilov, Svetlana Bozhkova, Andrey Sereda, Vitaliy Karelkin, Natella Enukashvily, Anna Malashicheva

{"title":"Mesenchymal Cells Retain the Specificity of Embryonal Origin During Osteogenic Differentiation.","authors":"Arseniy Lobov, Polina Kuchur, Aigul Khizhina, Anastasia Kotova, Andrei Ivashkin, Daria Kostina, Polina Klausen, Evgeniia Khokhlova, Egor Repkin, Kseniia Postnikova, Daria Perepletchikova, Evgeny Denisov, Tatiana Gerashchenko, Rashid Tikhilov, Svetlana Bozhkova, Andrey Sereda, Vitaliy Karelkin, Natella Enukashvily, Anna Malashicheva","doi":"10.1093/stmcls/sxad081","DOIUrl":"10.1093/stmcls/sxad081","url":null,"abstract":"Mesenchymal stem cells (MSCs) are widely used in therapy, but the differences between MSCs of various origins and their ability to undergo osteogenic differentiation and produce extracellular matrix are not fully understood. To address this, we conducted a comparative analysis of mesenchymal cell primary cultures from 6 human sources, including osteoblast-like cells from the adult femur, adipose-derived stem cells, Wharton's jelly-derived mesenchymal cells, gingival fibroblasts, dental pulp stem cells, and periodontal ligament stem cells. We analyzed these cells' secretome, proteome, and transcriptome under standard and osteogenic cultivation conditions. Despite the overall similarity in osteogenic differentiation, the cells maintain their embryonic specificity after isolation and differentiation in vitro. Furthermore, we propose classifying mesenchymal cells into 3 groups: dental stem cells of neural crest origin, mesenchymal stem cells, and fetal stem cells. Specifically, fetal stem cells have the most promising secretome for various applications, while mesenchymal stem cells have a specialized secretome optimal for extracellular matrix production. Nevertheless, mesenchymal cells from all sources secreted core bone extracellular matrix-associated proteins. In conclusion, our study illuminates the distinctive characteristics of mesenchymal stem cells from various sources, providing insights into their potential applications in regenerative medicine and enhancing our understanding of the inherent diversity of mesenchymal cells in vivo.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"76-89"},"PeriodicalIF":5.2,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476064","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

Selective Inhibition of mTORC1 Signaling Supports the Development and Maintenance of Pluripotency. 选择性抑制mTORC1信号传导支持多能性的发展和维持。

IF 4 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad079

Jin Koo Kim, Luis G Villa-Diaz, Thomas L Saunders, Ruiz P Saul, Suraj Timilsina, Fei Liu, Yuji Mishina, Paul H Krebsbach

引用次数: 0

O-Linked N-Acetylglucosamine Transferase Ensures Survival of Mouse Fetal Liver Hematopoietic Progenitors Partly by Regulating Bcl-xL and Oxidative Phosphorylation. OGT部分通过调节Bcl-xL和氧化磷酸化来确保小鼠胎肝造血祖细胞的存活。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-01-13 DOI: 10.1093/stmcls/sxad076

Shunsuke Soma, Koichi Murakami, Yumi Fukuchi, Hiroyoshi Kunimoto, Hideaki Nakajima

{"title":"O-Linked N-Acetylglucosamine Transferase Ensures Survival of Mouse Fetal Liver Hematopoietic Progenitors Partly by Regulating Bcl-xL and Oxidative Phosphorylation.","authors":"Shunsuke Soma, Koichi Murakami, Yumi Fukuchi, Hiroyoshi Kunimoto, Hideaki Nakajima","doi":"10.1093/stmcls/sxad076","DOIUrl":"10.1093/stmcls/sxad076","url":null,"abstract":"O-linked N-acetylglucosamine transferase (OGT) critically regulates wide variety of biological processes such as gene expression, metabolism, stress response, signaling and proteostasis. In adult hematopoiesis, OGT is crucial for differentiation of B and T cells and the maintenance of hematopoietic stem cells (HSCs). However, a role for OGT in fetal liver (FL) hematopoiesis remains unknown. To investigate a role for OGT in FL hematopoiesis, we conditionally disrupted OGT in hematopoietic cells in developing FLs. Hematopoietic specific disruption of OGT resulted in embryonic lethality in late stage of gestation due to severe anemia and growth retardation. OGT loss led to profound reduction of differentiating erythroid cells and erythroid progenitors in FLs due to massive apoptosis. In addition, clonogenic capacity of FL cells was severely impaired by OGT loss. Interestingly, expression of BCL-XL, a well-known inhibitor of apoptosis in FL cells, dramatically decreased, and the levels of reactive oxygen species (ROS) were increased in OGT-deficient FL cells. Overexpression of Bcl-xL and reduction of ROS significantly restored the colony formation of OGT-deficient FL cells. This study revealed a novel role for OGT during embryogenesis, which ensures survival of FL hematopoietic cells partly by regulating Bcl-xL and oxidative phosphorylation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"55-63"},"PeriodicalIF":5.2,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41181581","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

Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling. 间充质干细胞通过 Mertk/JAK1/STAT6 信号传导促进急性慢性肝衰竭小鼠 M2 巨噬细胞的极化

IF 5.2 2区医学

STEM CELLS Pub Date : 2023-12-14 DOI: 10.1093/stmcls/sxad069

Zhi-Hui Li, Jun-Feng Chen, Jing Zhang, Zi-Ying Lei, Li-Li Wu, Shi-Bo Meng, Jia-Lei Wang, Jing Xiong, Deng-Na Lin, Jun-Yi Wang, Zhi-Liang Gao, Bing-Liang Lin

{"title":"Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling.","authors":"Zhi-Hui Li, Jun-Feng Chen, Jing Zhang, Zi-Ying Lei, Li-Li Wu, Shi-Bo Meng, Jia-Lei Wang, Jing Xiong, Deng-Na Lin, Jun-Yi Wang, Zhi-Liang Gao, Bing-Liang Lin","doi":"10.1093/stmcls/sxad069","DOIUrl":"10.1093/stmcls/sxad069","url":null,"abstract":"Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1171-1184"},"PeriodicalIF":5.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10140836","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