Rab5c-mediated Endocytic Trafficking Regulates Hematopoietic Stem and Progenitor Cell Development Via Notch and AKT Signaling

Overview

Journal PLoS Biol

Specialty Biology

Date 2020 Apr 11

PMID 32275659

Citations 14

Authors

Jian Heng

Peng Lv

Yifan Zhang

Xinjie Cheng

Lu Wang

Dongyuan Ma

Feng Liu

Affiliations

Soon will be listed here.

Abstract

It is well known that various developmental signals play diverse roles in hematopoietic stem and progenitor cell (HSPC) production; however, how these signaling pathways are orchestrated remains incompletely understood. Here, we report that Rab5c is essential for HSPC specification by endocytic trafficking of Notch and AKT signaling in zebrafish embryos. Rab5c deficiency leads to defects in HSPC production. Mechanistically, Rab5c regulates hemogenic endothelium (HE) specification by endocytic trafficking of Notch ligands and receptor. We further show that the interaction between Rab5c and Appl1 in the endosome is required for the survival of HE in the ventral wall of the dorsal aorta through AKT signaling. Interestingly, Rab5c overactivation can also lead to defects in HSPC production, which is attributed to excessive endolysosomal trafficking inducing Notch signaling defect. Taken together, our findings establish a previously unrecognized role of Rab5c-mediated endocytic trafficking in HSPC development and provide new insights into how spatiotemporal signals are orchestrated to accurately execute cell fate transition.

Citing Articles

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