Rab5c-Mediated Endocytic Trafficking Regulates Hematopoietic Stem and Progenitor Cell Development via Notch and AKT Signaling

    April 2020 in “ PLoS Biology ”
    Jian Heng, Peng Lv, Yifan Zhang, Xinjie Cheng, Lu Wang, Dongyuan Ma, Feng Liu
    TLDR Rab5c is crucial for blood stem cell development by regulating Notch and AKT signals.
    The study revealed that Rab5c played a crucial role in the development of hematopoietic stem and progenitor cells (HSPCs) in zebrafish embryos by mediating endocytic trafficking of Notch and AKT signaling. Rab5c deficiency resulted in impaired HSPC production due to disrupted hemogenic endothelium (HE) specification. The interaction between Rab5c and Appl1 in the endosome was necessary for HE survival via AKT signaling. However, overactivation of Rab5c also caused defects in HSPC production due to excessive endolysosomal trafficking, leading to Notch signaling defects. These findings highlighted the importance of Rab5c-mediated endocytic trafficking in HSPC development and provided insights into the orchestration of developmental signals for cell fate transition.
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