Pulse Activation of Retinoic Acid Receptor Enhances Hematopoietic Stem Cell Homing by Controlling CXCR4 Membrane Presentation.

IF 4.5 3区医学 Q2 CELL & TISSUE ENGINEERING Stem Cell Reviews and Reports Pub Date : 2024-10-31 DOI:10.1007/s12015-024-10813-4

Nanxi Geng, Ziqin Yu, Xingchao Zeng, Yuxuan Chen, Mengyao Sheng, Danhua Xu, Menghong Yan, Min Yang, Xinxin Huang

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Abstract

The interplay between metabolic signaling and stem cell biology has gained increasing attention, though the underlying molecular mechanisms remain incompletely elucidated. In this study, we identify and characterize the role of adapalene (ADA), a retinoic acid receptor (RAR) agonist, in modulating the migration behavior of hematopoietic stem cells (HSCs). Our initial findings reveal that ADA treatment suppresses hematopoietic stem and progenitor cell (HSPC) mobilization induced by AMD3100 and G-CSF. Furthermore, we demonstrate that ADA treatment upregulates the surface expression of CXCR4 on HSPCs, resulting in enhanced chemotaxis towards CXCL12. Mechanistically, our study suggests that ADA enhances CXCR4 surface presentation without increasing CXCR4 mRNA levels, pointing towards a non-canonical role of RAR signaling in regulating intracellular trafficking of CXCR4. In vivo experiments show that ADA administration significantly enhances HSC homing efficiency. Additionally, competitive transplantation assays indicate a marked increase in donor chimerism following ADA treatment. These findings highlight the critical role of retinoic acid signaling in regulating HSC homing and suggest its potential for advancing novel HSC-based therapeutic strategies.

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视黄酸受体的脉冲激活通过控制 CXCR4 的膜呈现增强造血干细胞的归巢能力

新陈代谢信号传导与干细胞生物学之间的相互作用日益受到关注，但其潜在的分子机制仍未完全阐明。在本研究中，我们确定并描述了视黄酸受体（RAR）激动剂阿达帕林（ADA）在调节造血干细胞（HSCs）迁移行为中的作用。我们的初步研究结果表明，ADA处理可抑制AMD3100和G-CSF诱导的造血干细胞和祖细胞（HSPC）迁移。此外，我们还证明，ADA治疗可上调造血干细胞表面CXCR4的表达，从而增强对CXCL12的趋化作用。从机理上讲，我们的研究表明 ADA 在不增加 CXCR4 mRNA 水平的情况下增强了 CXCR4 的表面表达，这表明 RAR 信号在调节 CXCR4 细胞内运输中的非经典作用。体内实验表明，ADA 能显著提高造血干细胞的归巢效率。此外，竞争性移植试验表明，ADA 治疗后供体嵌合率明显提高。这些发现凸显了视黄酸信号在调节造血干细胞归巢中的关键作用，并表明视黄酸信号在推进基于造血干细胞的新型治疗策略方面具有潜力。

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来源期刊

Stem Cell Reviews and Reports 医学-细胞生物学

CiteScore

9.30

自引率

4.20%

发文量

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.