Chemical Cocktail Induces Hematopoietic Reprogramming and Expands Hematopoietic Stem/Progenitor Cells
Chemical Cocktail Induces Hematopoietic Reprogramming and Expands Hematopoietic Stem/Progenitor Cells
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化学混合物诱导造血重编程并扩增造血干/祖细胞
DOI：
10.1002/advs.201901785
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发表时间：
2019-11-11
期刊：
影响因子：
15.1
通讯作者：
Cheng, Lin
中科院分区：
文献类型：
--
作者：
Zhou, Yi;Zhu, Xingli;Cheng, Lin
通过细胞扩增或细胞重编程产生造血干/祖细胞（HSPC）已通过转录因子的过表达广泛实现。在此，据报道，在不引入外源基因的情况下，小鼠成纤维细胞可以基于谱系追踪分析重编程为生血细胞，其通过化合物的混合物处理进一步发育为造血细胞。化学鸡尾酒还将分化的造血细胞重新编程为HSPC样细胞。最重要的是，能够实现造血重编程的化学混合物强烈促进HSPC离体增殖。扩增的HSPCs在体内获得增强的造血重建能力。单细胞测序分析验证了HSPC的扩增和细胞重编程，同时通过化学鸡尾酒处理朝向HSPC的潜在产生。因此，概念验证的发现不仅证明了造血重编程可以通过化合物实现，而且还提供了一种有前途的策略，用于通过化学鸡尾酒激活的双重效应获得HSPC。
Generation of hematopoietic stem/progenitor cells (HSPCs) via cell expansion or cell reprogramming has been widely achieved by overexpression of transcription factors. Herein, it is reported that without introducing exogenous genes, mouse fibroblasts can be reprogrammed into hemogenic cells based on lineage tracing analysis, which further develop into hematopoietic cells, by treatment of cocktails of chemical compounds. The chemical cocktails also reprogram differentiated hematopoietic cells back into HSPC-like cells. Most importantly, the chemical cocktails enabling hematopoietic reprogramming robustly promote HSPC proliferation ex vivo. The expanded HSPCs acquire enhanced capacity of hematopoietic reconstruction in vivo. Single-cell sequencing analysis verifies the expansion of HSPCs and the cell reprogramming toward potential generation of HSPCs at the same time by the chemical cocktail treatment. Thus, the proof-of-concept findings not only demonstrate that hematopoietic reprogramming can be achieved by chemical compounds but also provide a promising strategy for acquisition of HSPCs by chemical cocktail-enabled double effects.