Geng Nanxi, Yu Ziqin, Zeng Xingchao, Chen Yuxuan, Sheng Mengyao, Xu Danhua, Yan Menghong, Yang Min, Huang Xinxin
Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and The Shanghai Key Laboratory of Medical Epigenetics, The International Co-Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Pudong Medical Center, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Stem Cell Rev Rep. 2025 Jan;21(1):68-79. doi: 10.1007/s12015-024-10813-4. Epub 2024 Oct 31.
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.
代谢信号与干细胞生物学之间的相互作用已受到越来越多的关注，但其潜在的分子机制仍未完全阐明。在本研究中，我们鉴定并表征了维甲酸受体（RAR）激动剂阿达帕林（ADA）在调节造血干细胞（HSC）迁移行为中的作用。我们的初步研究结果显示，ADA处理可抑制AMD3100和G-CSF诱导的造血干祖细胞（HSPC）动员。此外，我们证明ADA处理可上调HSPC表面CXCR4的表达，从而增强对CXCL12的趋化性。从机制上讲，我们的研究表明，ADA可增强CXCR4的表面呈现，而不增加CXCR4 mRNA水平，这表明RAR信号在调节CXCR4细胞内运输中具有非经典作用。体内实验表明，给予ADA可显著提高HSC归巢效率。此外，竞争性移植试验表明，ADA处理后供体嵌合率显著增加。这些发现突出了维甲酸信号在调节HSC归巢中的关键作用，并表明其在推进基于HSC的新型治疗策略方面的潜力。
