Trappc1 is essential for the maintenance and differentiation of common myeloid progenitors in mice

ABSTRACT: Trafficking protein particle complex (Trapp complex) is a highly conserved multi-unit protein machinery, and participates in intracellular vesicle traffic related process. Currently, little is known about Trapp complexes in the development of immune cells. Here，we uncovered the continuously up-regulated protein processing in endoplasmic reticulum during myeloid cell development by bioinformatics data mining, and identified trafficking protein particle complex subunit 1 (Trappc1,one of the core subunits of Trapp complexes) as an indispensable master for myeloid cell development. By using the ER-Trappc1 inducible knockout mice and bone marrow chimeric mouse models and in vitro experiments, we demonstrated that the deficiency of Trappc1 led to a sever defect of myeloid cells, including monocytes and neutrophils, resulting from dramatic loss and retardation of common myeloid progenitors (CMPs) differentiation. Mechanistically, Trappc1-depleted CMPs suffered from an irreparable endoplasmic reticulum stress, and underwent apoptosis via Ca2+ mitochondrial dependent pathway. Meanwhile, the depletion of Trappc1 caused the cell cycle arrest and cellular senescence of CMPs by activation of pancreatic endoplasmic reticulum kinase (PERK) and downstream up-regulation of cyclin-dependent kinase inhibitor p21. The proliferation stagnation and elevated apoptosis of CMPs conspired to cause the defect of myeloid cell development. These findings reveal the essential role of Trappc1 in the maintenance and differentiation of CMPs, and contributes to existing knowledge of the significancy endoplasmic reticulum homeostasis during myeloid cell development.

ORGANISM(S): Mus musculus

PROVIDER: GSE201077 | GEO | 2022/04/26

REPOSITORIES: GEO