Murine and Human-Purified very Small Embryonic-like Stem Cells (VSELs) Express Purinergic Receptors and Migrate to Extracellular ATP Gradient

IF 4.5 3区 医学 Q2 CELL & TISSUE ENGINEERING Stem Cell Reviews and Reports Pub Date : 2024-04-18 DOI:10.1007/s12015-024-10716-4
Kamila Bujko, Katarzyna Brzezniakiewicz-Janus, Justyna Jarczak, Magdalena Kucia, Mariusz Z. Ratajczak
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Abstract

Purinergic signaling is an ancient primordial signaling system regulating tissue development and specification of various types of stem cells. Thus, functional purinergic receptors are present in several types of cells in the body, including multiple populations of stem cells. However, one stem cell type that has not been evaluated for expression of purinergic receptors is very small embryonic stem cells (VSELs) isolated from postnatal tissues. Herein, we report that human umbilical cord blood (UCB) and murine bone marrow (BM) purified VSELs express mRNA for P1 and P2 purinergic receptors and CD39 and CD73 ectonucleotidases converting extracellular ATP (eATP) into its signaling metabolite extracellular adenosine (eAdo), that antagonizes eATP effects. More importantly, we demonstrate that human and murine VSELs respond by chemotaxis to eATP, and eAdo inhibits this migration. These responses to eATP are mediated by activation of Nlrp3 inflammasome, and exposure of VSELs to its specific inhibitor MCC950 abolished the chemotactic response to ATP. We conclude that purinergic signaling plays an essential, underappreciated role in the biology of these cells and their potential role in response to tissue/organ injuries.

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小鼠和人类纯化的极小胚胎样干细胞 (VSEL) 表达嘌呤能受体并向细胞外 ATP 梯度迁移
嘌呤能信号是一种古老的原始信号系统,它调节组织发育和各类干细胞的规格。因此,功能性嘌呤能受体存在于体内多种类型的细胞中,包括多种干细胞群。然而,从出生后组织中分离出的极小胚胎干细胞(VSELs)是一种尚未进行嘌呤能受体表达评估的干细胞类型。在此,我们报告了人脐带血(UCB)和小鼠骨髓(BM)纯化的VSELs表达P1和P2嘌呤能受体的mRNA以及CD39和CD73外切核苷酸酶,它们能将细胞外ATP(eATP)转化为其信号代谢产物细胞外腺苷(eAdo),从而拮抗eATP的作用。更重要的是,我们证明了人类和鼠类 VSEL 对 eATP 的趋化反应,而 eAdo 可抑制这种迁移。这些对eATP的反应是由Nlrp3炎性体的激活介导的,而将VSEL暴露于其特异性抑制剂MCC950中会取消对ATP的趋化反应。我们的结论是,嘌呤能信号在这些细胞的生物学及其对组织/器官损伤的潜在反应中发挥着重要的、未被充分认识的作用。
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来源期刊
Stem Cell Reviews and Reports
Stem Cell Reviews and Reports 医学-细胞生物学
CiteScore
9.30
自引率
4.20%
发文量
0
审稿时长
3 months
期刊介绍: The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication: i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field. ii) full length and short reports presenting original experimental work. iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics. iv) papers focused on diseases of stem cells. v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale. vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research. vii) letters to the editor and correspondence. In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on: i) the role of adult stem cells in tissue regeneration; ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development; iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells; iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis; v) the role of stem cells in aging processes and cancerogenesis.
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