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Abstract：
Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium (HE) in the aorta- gonads-and mesonephros (AGM) region and reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). The signalling mechanisms that distinguish HSCs from HPCs are unknown. Notch signaling is essential for arterial specification, IAHC formation and HSC activity, but current studies on how Notch segregates these different fates are inconsistent. We now demonstrate that Notch activity is highest in a subset of, GFI1 + , HSC-primed HE cells, and is gradually lost with HSC maturation. We uncover that the HSC phenotype is maintained due to increasing levels of NOTCH1 and JAG1 interactions on the surface of the same cell (cis) that renders the NOTCH1 receptor from being activated. Forced activation of the NOTCH1 receptor in IAHC activates a hematopoietic differentiation program. Our results indicate that NOTCH1-JAG1 cis-inhibition preserves the HSC phenotype in the hematopoietic clusters of the embryonic aorta.
摘要：
造血干细胞(HSC)从主动脉-性腺-和中肾(AGM)区域中的生血内皮(HE)发育,并与造血祖细胞(HPC)一起存在于主动脉内造血簇(IAHC)内。区分HSC和HPC的信号传导机制是未知的。Notch信号对动脉规范至关重要，IAHC形成和HSC活性，但是目前关于Notch如何将这些不同的命运分开的研究是不一致的。我们现在证明Notch活性在以下子集中最高，GFI1+,HSC引发的HE细胞，并且随着HSC成熟而逐渐丧失。我们发现，由于同一细胞表面上NOTCH1和JAG1相互作用水平的增加（顺式），导致NOTCH1受体被激活，因此HSC表型得以维持。IAHC中NOTCH1受体的强制激活激活造血分化程序。我们的结果表明，NOTCH1-JAG1顺式抑制保留了胚胎主动脉造血簇中的HSC表型。
