Zhou Yi, Wei Chuijin, Xiong Shumin, Dong Liaoliao, Chen Zhu, Chen Sai-Juan, Cheng Lin
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
J Hematol Oncol. 2020 Dec 10;13(1):171. doi: 10.1186/s13045-020-01008-8.
Hematopoietic reprogramming holds great promise for generating functional target cells and provides new angle for understanding hematopoiesis. We reported before for the first time that diverse differentiated hematopoietic cell lineages could be reprogrammed back into hematopoietic stem/progenitor cell-like cells by chemical cocktail. However, the exact cell types of induced cells and reprogramming trajectory remain elusive. Here, based on genetic tracing method CellTagging and single-cell RNA sequencing, it is found that neutrophils could be reprogrammed into multipotent progenitors, which acquire multi-differentiation potential both in vitro and in vivo, including into lymphoid cells. Construction of trajectory map of the reprogramming procession shows that mature neutrophils follow their canonical developmental route reversely into immature ones, premature ones, granulocyte/monocyte progenitors, common myeloid progenitors, and then the terminal cells, which is stage by stage or skips intermediate stages. Collectively, this study provides a precise dissection of hematopoietic reprogramming procession and sheds light on chemical cocktail-induction of hematopoietic stem cells.
造血重编程在生成功能性靶细胞方面具有巨大潜力，并为理解造血作用提供了新视角。我们之前首次报道，通过化学混合物可将多种分化的造血细胞谱系重编程回造血干/祖细胞样细胞。然而，诱导细胞的确切细胞类型和重编程轨迹仍不清楚。在此，基于基因追踪方法CellTagging和单细胞RNA测序，发现中性粒细胞可重编程为多能祖细胞，其在体外和体内均获得多向分化潜能，包括分化为淋巴细胞。重编程过程轨迹图的构建表明，成熟中性粒细胞沿着其经典发育路线逆向转变为未成熟中性粒细胞、早幼粒细胞、粒细胞/单核细胞祖细胞、常见髓系祖细胞，然后是终末细胞，这是一个逐阶段或跳过中间阶段的过程。总的来说，这项研究对造血重编程过程进行了精确剖析，并为化学混合物诱导造血干细胞提供了线索。
