He Wenyan, Zhang Ying, Cao Zhan, Ye Zehua, Lu Xun, Fan Junwan, Peng Wei, Li Zhuan
China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Front Cell Dev Biol. 2021 Sep 17;9:732527. doi: 10.3389/fcell.2021.732527. eCollection 2021.
The first adult repopulating hematopoietic stem cells (HSCs) are found in the aorta-gonad-mesonephros (AGM) region, which are produced from hemogenic endothelial cells. Embryonic head is the other site for HSC development. Wild-type p53-induced phosphatase 1 (Wip1) is a type-2Cδ family serine/threonine phosphatase involved in various cellular processes such as lymphoid development and differentiation of adult HSCs. Most recently, we have shown that Wip1 modulates the pre-HSC maturation in the AGM region. However, it is not clear whether Wip1 regulates hematopoiesis in the embryonic head. Here we reported that disruption of Wip1 resulted in a decrease of hematopoietic progenitor cell number in the embryonic head. transplantation assays showed a reduction of HSC function after Wip1 ablation. We established that Wip1 deletion reduced the frequency and cell number of microglia in the embryonic head. Further observations revealed that Wip1 absence enhanced the gene expression of microglia-derived pro-inflammatory factors. Thus, it is likely that Wip1 functions as a positive regulator in HSC development by regulating the function of microglia in the embryonic head.
首个可重新填充的成年造血干细胞（HSC）在主动脉-性腺-中肾（AGM）区域被发现，这些细胞由造血内皮细胞产生。胚胎头部是HSC发育的另一个位点。野生型p53诱导磷酸酶1（Wip1）是一种2Cδ家族丝氨酸/苏氨酸磷酸酶，参与多种细胞过程，如淋巴细胞发育和成年HSC的分化。最近，我们发现Wip1可调节AGM区域造血干细胞前体细胞的成熟。然而，Wip1是否调节胚胎头部的造血作用尚不清楚。在此我们报告，Wip1的缺失导致胚胎头部造血祖细胞数量减少。移植试验表明，Wip1缺失后HSC功能降低。我们证实，Wip1基因缺失减少了胚胎头部小胶质细胞的频率和数量。进一步观察发现，Wip1的缺失增强了小胶质细胞来源的促炎因子的基因表达。因此，Wip1可能通过调节胚胎头部小胶质细胞的功能，在HSC发育中发挥正向调节作用。
