4.7 Article

C/EBP homologous protein deficiency enhances hematopoietic stem cell function via reducing ATF3/ROS-induced cell apoptosis

期刊

AGING CELL
卷 20, 期 7, 页码 -

出版社

WILEY
DOI: 10.1111/acel.13382

关键词

apoptosis; ATF3; C; EBP homologous protein; hematopoietic stem cell function; ROS

资金

  1. National Natural Science Foundation of China [82030039]
  2. Natural Science Foundation of Guangdong Province, China [2020A1515010453]

向作者/读者索取更多资源

The research reveals a new role of CHOP in regulating HSCs function and homeostasis by reducing ATF3 and ROS signaling, leading to improved HSCs homeostasis and function.
Hematopoietic stem cells (HSCs) reside in a quiescent niche to reserve their capacity of self-renewal. Upon hematopoietic injuries, HSCs enter the cell cycle and encounter protein homeostasis problems caused by accumulation of misfolded proteins. However, the mechanism by which protein homeostasis influences HSC function and maintenance remains poorly understood. Here, we show that C/EBP homologous protein (CHOP), demonstrated previously to induces cell death upon unfolded protein response (UPR), plays an important role in HSCs regeneration. CHOP-/- mice showed normal hematopoietic stem and progenitor cell frequencies in steady state. However, when treated with 5-FU, CHOP deficiency resulted in higher survival rates, associated with an increased number of HSCs and reduced level of apoptosis. In serial competitive transplantation experiments, CHOP-/- HSCs showed a dramatic enhancement of repopulation ability and a reduction of protein aggresomes. Mechanistically, CHOP deletion causes reduced ATF3 expression and further leads to decreased protein aggregation and ROS. In addition, CHOP-/- HSCs exhibited an increased resistance to IR-induced DNA damage and improved HSCs homeostasis and function in telomere dysfunctional (G3Terc(-/-)) mice. In summary, these findings disclose a new role of CHOP in the regulation of the HSCs function and homeostasis through reducing ATF3 and ROS signaling.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据