Abstract
Hematopoietic stem cells (HSCs) can give rise to all blood cells that are essential to defend against pathogen invasion. The defective capability of HSC self-renewal is linked to many serious diseases, such as anemia. However, the potential mechanism regulating HSC self-renewal has not been thoroughly elucidated to date. In this study, we showed that Zfp90 was highly expressed in HSCs. Zfp90 deficiency in the hematopoietic system caused impaired HSPC pools and led to HSC dysfunction. We showed that Zfp90 deletion inhibited HSC proliferation, while HSC apoptosis was not affected. Regarding the mechanism of this effect on HSC proliferation, we found that Zfp90 interacted with Snf2l, a subunit of the NURF complex, to regulate Hoxa9 expression. Ectopic expression of Hoxa9 rescued the HSC repopulation capacity in Zfp90-deficient mice, which indicates that Hoxa9 is the downstream effector of Zfp90. In summary, our findings identify Zfp90 as a key transcription factor in determining the fate of HSCs.
Highlights
Hematopoietic stem cells (HSCs) generate all types of mature blood cells, which are essential for defense against pathogen infection
We found that Zfp[90] is highly expressed in HSCs compared with multipotent progenitor cells (MPP)
HSCs can differentiate toward multipotent progenitor cells (MPP) and MkE followed by common lymphoid progenitor cells (CLP) or common myeloid progenitor cells (CMP)[12,13]
Summary
Hematopoietic stem cells (HSCs) generate all types of mature blood cells, which are essential for defense against pathogen infection. HSCs mostly exist in a quiescent state, they can quickly expand and differentiate in response to intrinsic or extrinsic cues, such as infection[1]. HSCs must maintain a balance between self-renewal and differentiation to preserve a constant hematopoietic stem progenitor cell (HSPC) pool and enough terminal hematopoietic cells. Hematopoiesis is elaborately regulated by signals and transcription factors[2,3]. Disorder of the regulation network often leads to the abnormal proliferation of HSCs and symmetric division. Dysregulation of particular transcription factors may lead to HSC exhaustion
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