He Qiuping, Gao Suwei, Lv Junhua, Li Wei, Liu Feng
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, Hebei University, Baoding, PR China.
Exp Hematol. 2017 Jul;51:1-6.e2. doi: 10.1016/j.exphem.2017.03.002. Epub 2017 Apr 27.
During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) after their emergence in the aorta-gonad-mesonephros (AGM) region. We recently reported that the endolysosomal trafficking factor BLOS2, encoded by the Bloc1s2 gene, regulates HSC/hematopoietic progenitor cell emergence in the AGM region; however, whether it plays a role in the FL remains unknown. Here, we show that BLOS2 plays an essential role in the regulation of HSC proliferation and differentiation in the FL. Bloc1s2 depletion leads to elevated Notch signaling, with an increased frequency but weakened self-renewal ability of FL HSCs. Functional assays show that Bloc1s2 FL HSCs harbor impaired lymphoid and myeloid differentiation abilities. These findings reveal that balanced control of Notch signaling by BLOS2 is required for HSC homeostasis during FL hematopoiesis.
在发育过程中，造血干细胞（HSCs）在主动脉-性腺-中肾（AGM）区域出现后，会在胎肝（FL）中迅速扩增。我们最近报道，由Bloc1s2基因编码的内溶酶体运输因子BLOS2调节AGM区域中HSC/造血祖细胞的出现；然而，它是否在胎肝中发挥作用仍不清楚。在这里，我们表明BLOS2在胎肝中HSC增殖和分化的调节中起重要作用。Bloc1s2缺失导致Notch信号升高，胎肝HSCs的频率增加但自我更新能力减弱。功能分析表明，Bloc1s2缺失的胎肝HSCs的淋巴样和髓样分化能力受损。这些发现揭示，在胎肝造血过程中，BLOS2对Notch信号的平衡控制是HSC稳态所必需的。
