BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development
BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development
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BLOS2 在神经和造血干细胞和祖细胞发育过程中负向调节 Notch 信号传导
作者：
Zhou Wenwen;He Qiuping;Zhang Chunxia;He Xin;Cui Zongbin;Liu Feng;Li Wei
Notch信号在胚胎发生或器官发生过程中控制干细胞和祖细胞的增殖和分化中发挥着至关重要的作用，但其调控机制尚不完全清楚。 BLOS2 由 Bloc1s2 基因编码，是两个溶酶体运输复合物、溶酶体相关细胞器复合物 - 1 (BLOC-1) 和 BLOC-1 相关复合物 (BORC) 生物发生的共享亚基。 Bloc1s2−/− 小鼠胚胎死亡，并表现出皮质发育和造血缺陷。 BLOS2 的缺失导致 Notch 信号传导增强，从而增加神经祖细胞的增殖并抑制皮质中的神经元分化。同样，斑马鱼或小鼠中 bloc1s2 的消融导致主动脉-性腺-中肾区域的造血干细胞和祖细胞产量增加。 BLOS2 在 Notch1 的内溶酶体运输中与 Notch1 发生物理相互作用。我们的研究结果表明，BLOS2 是通过溶酶体运输调节 Notch 信号传导以控制脊椎动物中多个干细胞和祖细胞稳态的新型负面参与者。 DOI：http://dx.doi.org/10.7554/eLife.18108.001
Notch signaling plays a crucial role in controling the proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related complex (BORC). Bloc1s2−/− mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation of bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking to control multiple stem and progenitor cell homeostasis in vertebrates. DOI: http://dx.doi.org/10.7554/eLife.18108.001
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