Spliceosome inhibitor induces human hematopoietic progenitor cell reprogramming toward stemness

作者：Liaoliao Dong, Chuijin Wei, Shu-Min Xiong, Ping Yu, Ren Zhou, Lin Cheng · 发表于：Experimental Hematology and Oncology · 年份：2022 · DOI：10.1186/s40164-022-00288-9 · 被引用次数：6 · 研究领域：Pluripotent Stem Cells Research、CRISPR and Genetic Engineering、Single-cell and spatial transcriptomics

The application of hematopoietic stem cells (HSCs) has been restricted due to limited cell sources and conventional methods for generating these cells by cell expansion and pluripotent stem cell differentiation have not been clinically achieved. Cell reprogramming technique provides a new hope for generating desirable cells. We previously reported that mouse differentiated hematopoietic cell reprogramming could be induced by small molecule compounds to generate hematopoietic stem/progenitor-like cells, whether the human hematopoietic cells could also be reprogrammed into HSCs by chemical compounds remains elusive. Here, we demonstrated for the first time that human committed hematopoietic progenitors could be reprogrammed into multipotent progenitors by spliceosome inhibitor. Combination of single cell RNA-sequencing and genetic lineage tracing including exogenous barcodes and endogenous mitochondrial DNA mutations confirmed the reprogramming procession. Although the small chemical compound inhibiting spliceosome function only induces the differentiated hematopoietic progenitors to acquire plasticity and reprograms them into multipotent progenitors but not stem cells so far, this study still provides a proof-of-concept strategy for generating HSCs based on combining two independent steps together in future, first differentiating rare HSCs into large number of progenitors then reprogramming these progenitors into huge number of HSCs. Further dissecting the mechanism underlying...