作者
Theodore T Ho, Matthew R Warr, Emmalee R Adelman, Olivia M Lansinger, Johanna Flach, Evgenia V Verovskaya, Maria E Figueroa, Emmanuelle Passegué
发表日期
2017/3/9
期刊
Nature
卷号
543
期号
7644
页码范围
205-210
出版商
Nature Publishing Group UK
简介
With age, haematopoietic stem cells lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting haematopoietic stem cells from metabolic stress. Here we show that loss of autophagy in haematopoietic stem cells causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs haematopoietic stem-cell self-renewal activity and regenerative potential. Strikingly, most haematopoietic stem cells in aged mice share these altered metabolic and functional features. However, approximately one-third of aged haematopoietic stem cells exhibit high autophagy levels and maintain a low metabolic state with robust long-term regeneration potential similar to healthy young haematopoietic stem cells. Our results …
学术搜索中的文章
TT Ho, MR Warr, ER Adelman, OM Lansinger, J Flach… - Nature, 2017