PDF(Pubmed)
Abstract：
Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a stem cell agonist in AA2P and optimize a series of stem cell agonist cocktails (SCACs) to help promote robust expansion of human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention and function of immature HSPC. We show that AA2P-mediated HSPC expansion is driven through DNA demethylation leading to enhanced expression of AXL and GAS6. Further, we demonstrate that GAS6 enhances the serial engraftment activity of HSPCs and show that the GAS6/AXL pathway is critical for robust HSPC expansion.
摘要：
小分子能够扩增造血干细胞和祖细胞（HSPC），但是关于这些激动剂是否可以协同作用的知识有限。在这项工作中,我们在AA2P中鉴定了一种干细胞激动剂,并优化了一系列干细胞激动剂混合物(SCACs),以帮助促进人HSPCs的强劲扩增.我们发现SCAC提供了强大的促进生长的活性，同时促进了未成熟HSPC的保留和功能。我们表明，AA2P介导的HSPC扩增是通过DNA去甲基化驱动的，从而导致AXL和GAS6的表达增强。Further,我们证明了GAS6增强了HSPC的连续植入活性，并表明GAS6/AXL途径对于强大的HSPC扩增至关重要。
