SRSF1 Regulates Hematopoietic Differentiation of Human Embryonic Stem Cells
HUANG Xin, WANG Ding, TONG Jingyuan, GAO Jie, LIU Jinhua, LI Yapu*, SHI Lihong*
Alternative splicing is a post-transcriptional process which impacts cell fate decision and lineage differentiation via regulating cell proliferation and differentiation. The prior study revealed splicing factor SRSF2 modulated the generation of HE (hemogenic endothelial cells) mainly through alternative splicing of NUMB transcripts during inducing hematopoietic differentiation from hESCs (human embryonic stem cells). Despite SRSF1 shared the similar expression pattern as SRSF2, its role in early hematopoietic differentiation is still largely unknown. In order to explore whether SRSF1 affects the production of HE during hematopoietic differentiation, this study constructed an inducible stable cell line of hESCs with overexpressed SRSF1 and found that overexpression of SRSF1 promoted the production of HE. In addition, knockdown of SRSF1 during the generation of HE by RNA interference technology can inhibit the production of HE. SRSF1 can bind to NUMB exon 9 and promote the production of NUMB short isoform, which were confirmed by the vitro alternative splicing reporter system. This study
confirmed that SRSF1 could affect the production of hemogenic endothelial cells, possibly by regulating the alternative splicing of NUMB.
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