Zhou Yi, Zhu Xingli, Dai Yuting, Xiong Shumin, Wei Chuijin, Yu Pei, Tang Yuewen, Wu Liang, Li Jianfeng, Liu Dan, Wang Yanlin, Chen Zhu, Chen Sai-Juan, Huang Jinyan, Cheng Lin
State Key Laboratory of Medical Genomics Shanghai Institute of Hematology Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine Shanghai Center for Systems Biomedicine Shanghai Jiao Tong University Shanghai 200025 China.
School of Life Sciences and Biotechnology Shanghai Jiao Tong University 200025 Shanghai China.
Adv Sci (Weinh). 2019 Nov 11;7(1):1901785. doi: 10.1002/advs.201901785. eCollection 2020 Jan.
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.
通过转录因子的过表达，经由细胞扩增或细胞重编程来生成造血干/祖细胞（HSPCs）已被广泛实现。在此报告中，基于谱系追踪分析表明，在不引入外源基因的情况下，通过化学化合物组合处理，小鼠成纤维细胞可被重编程为造血细胞，进而进一步发育为造血细胞。这些化学化合物组合还能将分化的造血细胞重编程回HSPC样细胞。最重要的是，能够实现造血重编程的化学化合物组合在体外有力地促进了HSPC的增殖。扩增后的HSPC在体内获得了更强的造血重建能力。单细胞测序分析证实了化学化合物组合处理可同时实现HSPC的扩增以及细胞向潜在HSPC生成方向的重编程。因此，这些概念验证性发现不仅证明了可通过化学化合物实现造血重编程，还为通过具有双重效应的化学化合物组合获取HSPC提供了一种有前景的策略。
