Differentiation of fetal hematopoietic stem cells requires ARID4B to restrict autocrine KITLG/KIT-Src signaling.
Differentiation of fetal hematopoietic stem cells requires ARID4B to restrict autocrine KITLG/KIT-Src signaling.
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胎儿造血干细胞的分化需要ARID 4 B来限制自分泌KITLG/KIT-Src信号传导。
DOI：
10.1016/j.celrep.2021.110036
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发表时间：
2021-11-23
期刊：
影响因子：
8.8
通讯作者：
Wu MY
中科院分区：
文献类型：
--
作者：
Young IC;Wu B;Andricovich J;Chuang ST;Li R;Tzatsos A;Wu RC;Wu MY
Balance between the hematopoietic stem cell (HSC) duality to either possess self-renewal capacity or differentiate into multipotency progenitors (MPPs) is crucial for maintaining homeostasis of the hematopoietic stem/progenitor cell (HSPC) compartment. To retain the HSC self-renewal activity, KIT, a receptor tyrosine kinase, in HSCs is activated by its cognate ligand KITLG originating from niche cells. Here, we show that AT-rich interaction domain 4B (ARID4B) interferes with KITLG/KIT signaling, consequently allowing HSC differentiation. Conditional Arid4b knockout in mouse hematopoietic cells blocks fetal HSC differentiation, preventing hematopoiesis. Mechanistically, ARID4B-deficient HSCs self-express KITLG and overexpress KIT. As to downstream pathways of KITLG/KIT signaling, inhibition of Src family kinases rescues the HSC differentiation defect elicited by ARID4B loss. In summary, the intrinsic ARID4B-KITLG/KIT-Src axis is an HSPC regulatory program that enables the differentiation state, while KIT stimulation by KITLG from niche cells preserves the HSPC undifferentiated pool. Hematopoietic stem cells (HSCs) at the top of the hematopoietic hierarchy are able to self-renew and differentiate to mature blood cells. Young et al. report that an HSC self-control mechanism established by ARID4B ensures HSC differentiation. ARID4B-deficient HSCs produce KITLG to stimulate KIT, leading to blockage of HSC differentiation and eventual hematopoietic failure.
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DOI：
10.1002/stem.2604
发表时间：
2017-06
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Kokavec J;Zikmund T;Savvulidi F;Kulvait V;Edelmann W;Skoultchi AI;Stopka T
通讯作者：
Stopka T
DOI：
10.1126/science.aad0084
发表时间：
2016-01-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Khan JA;Mendelson A;Kunisaki Y;Birbrair A;Kou Y;Arnal-Estapé A;Pinho S;Ciero P;Nakahara F;Ma'ayan A;Bergman A;Merad M;Frenette PS
通讯作者：
Frenette PS
ARID 家族的最新进展：关注人类癌症中的作用
影响因子：
4
作者：
Lin C;Song W;Bi X;Zhao J;Huang Z;Li Z;Zhou J;Cai J;Zhao H
通讯作者：
Zhao H
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
56.9
作者：
Huang, Y;Fang, J;Xu, RM
通讯作者：
Xu, RM