ATF4 governs functional expansion of hematopoietic stem cells partially via Angptl3 in the fetal liver microenvironment (array)

In this study, we demonstrated that deletion of the activating transcription factor 4 (ATF4) resulted in severely impaired HSC expansion in the fetal liver at E12.5 and E15.5. In contrast, generation of the first HSC population in the aorta-gonad-mesonephros region at E11.5 was not significantly affected. Furthermore, the HSC-supporting ability of both endothelial and stromal cells in fetal liver was significantly compromised in the absence of ATF4. Gene profiling using RNA-seq revealed down-regulated expression of a panel of cytokines in ATF4-/- stromal cells, including angiopoietin-like protein 3 (Angptl3) and vascular endothelial growth factor-A (VEGFA).

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Zhao Y, Zhou J, Liu D, Dong F, Cheng H, Wang W, Pang Y, Wang Y, Mu X, Ni Y, Li Z, Xu H, Hao S, Wang X, Ma S, Wang QF, Xiao G, Yuan W, Liu B, Cheng T