STEM CELLS最新文献_第10页

Leucine-Rich Repeat Containing 15-Mediated Cell Adhesion Is Essential for Integrin Signaling in TGF-β1-Induced PDL Fibroblastic Differentiation. 在 TGF-β1 诱导的 PDL 成纤维细胞分化过程中，富亮氨酸重复序列 15 (LRRC15) 介导的细胞粘附对整合素信号转导至关重要。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-03-14 DOI: 10.1093/stmcls/sxad090

Hyun-Jin Kim, Dong-Jun Kim, Seong-Min Kim, Young-Joo Jang

{"title":"Leucine-Rich Repeat Containing 15-Mediated Cell Adhesion Is Essential for Integrin Signaling in TGF-β1-Induced PDL Fibroblastic Differentiation.","authors":"Hyun-Jin Kim, Dong-Jun Kim, Seong-Min Kim, Young-Joo Jang","doi":"10.1093/stmcls/sxad090","DOIUrl":"10.1093/stmcls/sxad090","url":null,"abstract":"Human periodontal ligament cells (hPDLCs) cultured from periodontal ligament (PDL) tissue contain postnatal stem cells that can be differentiated into PDL fibroblasts. We obtained PDL fibroblasts from hPDLCs by treatment with low concentrations of TGF-β1. Since the extracellular matrix and cell surface molecules play an important role in differentiation, we had previously developed a series of monoclonal antibodies against PDL fibroblast-specific cell surface molecules. One of these, the anti-PDL51 antibody, recognized a protein that was significantly upregulated in TGF-β1-induced PDL fibroblasts and highly accumulated in the PDL region of the tooth root. Mass spectrometry revealed that the antigen recognized by the anti-PDL51 antibody was leucine-rich repeat containing 15 (LRRC15), and this antibody specifically recognized the extracellular glycosylated moiety of LRRC15. Experiments presented here show that as fibroblastic differentiation progresses, increased amounts of LRRC15 localized at the cell surface and membrane. Inhibition of LRRC15 by siRNA-mediated depletion and by antibody blocking resulted in downregulation of the representative PDL fibroblastic markers. Moreover, following LRRC15 inhibition, the directed and elongated cell phenotypes disappeared, and the long processes of the end of the cell body were no longer found. Through a specific interaction between integrin β1 and LRRC15, the focal adhesion kinase signaling pathway was activated in PDL fibroblasts. Furthermore, it was shown that increased LRRC15 was important for the activation of the integrin-mediated cell adhesion signal pathway for regulation of cellular functions, including fibroblastic differentiation, proliferation, and cell migration arising from the expression of PDL-related genes in TGF-β1-induced PDL fibroblastic differentiation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"251-265"},"PeriodicalIF":5.2,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486313","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

Entropy Meets Physiology: Should We Translate Aging as Disorder? 熵与生理学的结合:我们应该将衰老解读为紊乱吗?

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad084

Marco Tatullo

{"title":"Entropy Meets Physiology: Should We Translate Aging as Disorder?","authors":"Marco Tatullo","doi":"10.1093/stmcls/sxad084","DOIUrl":"10.1093/stmcls/sxad084","url":null,"abstract":"Aging is characterized by an alteration of several physiological processes and biological pathways that leads to an increased susceptibility to age-related diseases and death. Normally, multipotential stem/progenitor cells may contribute to tissue homeostasis, and to minimize the age-depending DNA damage. Scientific research has demonstrated that aging induces several complex changes affecting even the mesenchymal stromal/stem cells (MSCs) ability to self-renew, differentiate, and immunomodulate the human tissues, causing further alterations in the local microenvironment. Cellular senescence can thus be considered as an overall response to several damages. Accordingly, aging seems to create the proper conditions to decrease the tissue's metabolic performance, and the cell-to-cell communication, resulting in a progressive tissue destruction; on the other hand, the MSCs functions appear to be severely reduced. This concise review summarizes the main alterations affecting the MSCs during aging, and it also explains the role of inflammation as a key player in age-related syndromes. The hypothesis is to suggest a parallelism between the thermodynamic concept of \"entropy\" and biological aging, speculating that both can increase within irreversible systems and both lead toward an irreversible disorder; so, the question is: should we translate aging as disorder?","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"91-97"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716253","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

BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway. BK通道耗竭通过激活MAPK/ERK通路促进脂肪细胞分化。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad082

Fang Xin, Yuan Cheng, Xinxin Wen, Jin Zhang, Xin Shi, Ping Liu, Jie Ren, Wenjing Lu, Fan Liu, Zihan Li, Xin Yan, Wei Wang, Meili Wang, Haixia Huang

{"title":"BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway.","authors":"Fang Xin, Yuan Cheng, Xinxin Wen, Jin Zhang, Xin Shi, Ping Liu, Jie Ren, Wenjing Lu, Fan Liu, Zihan Li, Xin Yan, Wei Wang, Meili Wang, Haixia Huang","doi":"10.1093/stmcls/sxad082","DOIUrl":"10.1093/stmcls/sxad082","url":null,"abstract":"The expression of large conductance calcium-activated potassium channels (BK channels) in adipose tissue has been identified for years. BK channel deletion can improve metabolism in vivo, but the relative mechanisms remain unclear. Here, we examined the effects of BK channels on the differentiation of adipose-derived stem cells (ADSCs) and the related mechanisms. BKα and β1 subunits were expressed on adipocytes. We found that both deletion of the KCNMA1 gene, encoding the pore forming α subunit of BK channels, and the BK channel inhibitor paxilline increased the expression of key genes in the peroxisome proliferator activated receptor (PPAR) pathway and promoted adipogenetic differentiation of ADSCs. We also observed that the MAPK-ERK pathway participates in BK channel deficiency-promoted adipogenic differentiation of ADSCs and that ERK inhibitors blocked the differentiation-promoting effect of BK channel deficiency. Hyperplasia of adipocytes is considered beneficial for metabolic health. These results indicate that BK channels play an important role in adipose hyperplasia by regulating the differentiation of ADSCs and may become an important target for studying the pathogenesis and treatment strategies of metabolic disorder-related diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"146-157"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716252","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

Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells. 烟酰胺核苷调节HIF-1信号传导以维持和增强人牙髓干细胞成牙细胞分化。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad083

Peimeng Zhan, Xinfang Zhang, Zhuo Xie, Lingling Chen, Shuheng Huang, Qiting Huang, Zhengmei Lin, Runfu Wang

{"title":"Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells.","authors":"Peimeng Zhan, Xinfang Zhang, Zhuo Xie, Lingling Chen, Shuheng Huang, Qiting Huang, Zhengmei Lin, Runfu Wang","doi":"10.1093/stmcls/sxad083","DOIUrl":"10.1093/stmcls/sxad083","url":null,"abstract":"Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"116-127"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716258","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 Damage Response After Treatment of Cycling and Quiescent Cord Blood Hematopoietic Stem Cells With Distinct Genotoxic Noxae. 不同基因毒性的脐带血造血干细胞循环和静止后的DNA损伤反应。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad085

Fabienne Becker, Meryem Ouzin, Stefanie Liedtke, Katharina Raba, Gesine Kogler

{"title":"DNA Damage Response After Treatment of Cycling and Quiescent Cord Blood Hematopoietic Stem Cells With Distinct Genotoxic Noxae.","authors":"Fabienne Becker, Meryem Ouzin, Stefanie Liedtke, Katharina Raba, Gesine Kogler","doi":"10.1093/stmcls/sxad085","DOIUrl":"10.1093/stmcls/sxad085","url":null,"abstract":"Hematopoietic stem cells (HSC) from cord blood can be applied as an alternative to bone marrow in transplantation to treat hematological diseases. Umbilical cord blood (UCB) consists of cycling and non-cycling CD34+/CD45low cells needed for long-term and short-term engraftment. After sorting and subsequent in vitro culture, quiescent HSCs enter the cell cycle. This enables the analysis of HSCs in 2 different cell cycle stages and the comparison of their responses to different genotoxic noxae. To analyze different mechanisms of DNA damage induction in cells, 2 different genotoxins were compared: etoposide, a topoisomerase II inhibitor that targets mitosis in the S/G2-phase of the cell cycle and the alkylating nitrosamine N-Nitroso-N-methylurea (MNU), which leads to the formation of methyl DNA adducts resulting in DNA double breaks during DNA replication and persistent mutations. Cycling cells recovered after treatment even with higher concentrations of etoposide (1.5µM/ 5µM/10µM), while sorted cells treated with MNU (0.1mM/0.3mM/0.5mM/1mM/3Mm/ 5mM) recovered after treatment with the lower MNU concentrations whereas high MNU concentrations resulted in apoptosis activation. Quiescent cells were not affected by etoposide treatment showing no damage upon entry into the cell cycle. Treatment with MNU, similarly to the cycling cells, resulted in a dose-dependent cell death. In conclusion, we found that depending on the genotoxic trigger and the cycling status, CD34+cells have distinct responses to DNA damage. Cycling cells employ both DDR and apoptosis mechanisms to prevent damage accumulation. Quiescent cells predominantly undergo apoptosis upon damage, but their cell cycle status protects them from certain genotoxic insults.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"158-171"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152062","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

Procoagulant Properties of Mesenchymal Stem Cells and Extracellular Vesicles: A Novel Aspect of Thrombosis Pathogenesis. 间充质干细胞和细胞外囊泡的促凝特性:血栓形成机制的一个新方面。

IF 5.2 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad087

Bianlei Yang, Yaoying Long, Anyuan Zhang, Hongxiang Wang, Zhichao Chen, Qiubai Li

{"title":"Procoagulant Properties of Mesenchymal Stem Cells and Extracellular Vesicles: A Novel Aspect of Thrombosis Pathogenesis.","authors":"Bianlei Yang, Yaoying Long, Anyuan Zhang, Hongxiang Wang, Zhichao Chen, Qiubai Li","doi":"10.1093/stmcls/sxad087","DOIUrl":"10.1093/stmcls/sxad087","url":null,"abstract":"Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and secrete extracellular vesicles (EVs) that transport bioactive molecules and mediate intercellular communication. MSCs and MSC-derived EVs (MSC-EVs) have shown promising therapeutic effects in several diseases. However, their procoagulant activity and thrombogenic risk may limit their clinical safety. In this review, we summarize current knowledge on procoagulant molecules expressed on the surface of MSCs and MSC-EVs, such as tissue factor and phosphatidylserine. Moreover, we discuss how these molecules interact with the coagulation system and contribute to thrombus formation through different mechanisms. Additionally, various confounding factors, such as cell dose, tissue source, passage number, and culture conditions of MSCs and subpopulations of MSC-EVs, affect the expression of procoagulant molecules and procoagulant activity of MSCs and MSC-EVs. Therefore, herein, we summarize several strategies to reduce the surface procoagulant activity of MSCs and MSC-EVs, thereby aiming to improve their safety profile for clinical use.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"98-106"},"PeriodicalIF":5.2,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648103","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

Vascularized Brain Assembloids With Enhanced Cellular Complexity Provide Insights Into the Cellular Deficits of Tauopathy. 增强细胞复杂性的血管化脑集合体为tau病的细胞缺陷提供了见解。

IF 4 2区医学

STEM CELLS Pub Date : 2024-02-08 DOI: 10.1093/stmcls/sxad086

Xiaohuan Sun, Simeon Kofman, Victor C Ogbolu, Celeste M Karch, Larisa Ibric, Liang Qiang

{"title":"Vascularized Brain Assembloids With Enhanced Cellular Complexity Provide Insights Into the Cellular Deficits of Tauopathy.","authors":"Xiaohuan Sun, Simeon Kofman, Victor C Ogbolu, Celeste M Karch, Larisa Ibric, Liang Qiang","doi":"10.1093/stmcls/sxad086","DOIUrl":"10.1093/stmcls/sxad086","url":null,"abstract":"Advanced technologies have enabled the engineering of self-organized 3-dimensional (3D) cellular structures from human induced pluripotent stem cells (hiPSCs), namely organoids, which recapitulate some key features of tissue development and functions of the human central nervous system (CNS). While hiPSC-derived 3D CNS organoids hold promise in providing a human-specific platform for studying CNS development and diseases, most of them do not incorporate the full range of implicated cell types, including vascular cell components and microglia, limiting their ability to accurately recreate the CNS environment and their utility in the study of certain aspects of the disease. Here we have developed a novel approach, called vascularized brain assembloids, for constructing hiPSC-derived 3D CNS structures with a higher level of cellular complexity. This is achieved by integrating forebrain organoids with common myeloid progenitors and phenotypically stabilized human umbilical vein endothelial cells (VeraVecs), which can be cultured and expanded in serum-free conditions. Compared with organoids, these assembloids exhibited enhanced neuroepithelial proliferation, advanced astrocytic maturation, and increased synapse numbers. Strikingly, the assembloids derived from hiPSCs harboring the tauP301S mutation exhibited increased levels of total tau and phosphorylated tau, along with a higher proportion of rod-like microglia-like cells and enhanced astrocytic activation, when compared to the assembloids derived from isogenic hiPSCs. Additionally, the tauP301S assembloids showed an altered profile of neuroinflammatory cytokines. This innovative assembloid technology serves as a compelling proof-of-concept model, opening new avenues for unraveling the intricate complexities of the human brain and accelerating progress in the development of effective treatments for neurological disorders.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"107-115"},"PeriodicalIF":4.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10852025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138297884","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

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