Details

Autor(en) / Beteiligte

• Xu, Longyong
• Liu, Xia
• Peng, Fanglue
• Zhang, Weijie
• Zheng, Liting
• Ding, Yao
• Gu, Tianpeng
• Lv, Kaosheng
• Wang, Jin
• Ortinau, Laura
• Hu, Tianyuan
• Shi, Xiangguo
• Shi, Guojun
• Shang, Ge
• Sun, Shengyi
• Iwawaki, Takao
• Ji, Yewei
• Li, Wei
• Rosen, Jeffrey M
• Zhang, Xiang H-F
• Park, Dongsu
• Adoro, Stanley
• Catic, Andre
• Tong, Wei
• Qi, Ling
• Nakada, Daisuke
• Chen, Xi

Titel

Protein quality control through endoplasmic reticulum-associated degradation maintains haematopoietic stem cell identity and niche interactions

Ist Teil von

• Nature cell biology, 2020-10, Vol.22 (10), p.1162-1169

Ort / Verlag

England

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Stem cells need to be protected from genotoxic and proteotoxic stress to maintain a healthy pool throughout life . Little is known about the proteostasis mechanism that safeguards stem cells. Here we report endoplasmic reticulum-associated degradation (ERAD) as a protein quality checkpoint that controls the haematopoietic stem cell (HSC)-niche interaction and determines the fate of HSCs. The SEL1L-HRD1 complex, the most conserved branch of ERAD , is highly expressed in HSCs. Deletion of Sel1l led to niche displacement of HSCs and a complete loss of HSC identity, and allowed highly efficient donor-HSC engraftment without irradiation. Mechanistic studies identified MPL, the master regulator of HSC identity , as a bona fide ERAD substrate that became aggregated in the endoplasmic reticulum following ERAD deficiency. Restoration of MPL signalling with an agonist partially rescued the number and reconstitution capacity of Sel1l-deficient HSCs. Our study defines ERAD as an essential proteostasis mechanism to safeguard a healthy stem cell pool by regulating the stem cell-niche interaction.