Chaperone-mediated autophagy sustains haematopoietic stem-cell function

Shuxian Dong, Qian Wang, Yun-Ruei Kao, Antonio Diaz, Inmaculada Tasset, Susmita Kaushik, Victor Thiruthuvanathan, Aliona Zintiridou, Edward Nieves, Monika Dzieciatkowska, Julie A. Reisz, Evripidis Gavathiotis, Angelo D’Alessandro, Britta Will () and Ana Maria Cuervo ()
Additional contact information
Shuxian Dong: Albert Einstein College of Medicine
Qian Wang: Albert Einstein College of Medicine
Yun-Ruei Kao: Albert Einstein College of Medicine
Antonio Diaz: Albert Einstein College of Medicine
Inmaculada Tasset: Albert Einstein College of Medicine
Susmita Kaushik: Albert Einstein College of Medicine
Victor Thiruthuvanathan: Albert Einstein College of Medicine
Aliona Zintiridou: Albert Einstein College of Medicine
Edward Nieves: Albert Einstein College of Medicine
Monika Dzieciatkowska: University of Colorado Denver – Anschutz Medical Campus
Julie A. Reisz: University of Colorado Denver – Anschutz Medical Campus
Evripidis Gavathiotis: Albert Einstein College of Medicine
Angelo D’Alessandro: University of Colorado Denver – Anschutz Medical Campus
Britta Will: Albert Einstein College of Medicine
Ana Maria Cuervo: Albert Einstein College of Medicine

Nature, 2021, vol. 591, issue 7848, 117-123

Abstract: Abstract The activation of mostly quiescent haematopoietic stem cells (HSCs) is a prerequisite for life-long production of blood cells1. This process requires major molecular adaptations to allow HSCs to meet the regulatory and metabolic requirements for cell division2–4. The mechanisms that govern cellular reprograming upon stem-cell activation, and the subsequent return of stem cells to quiescence, have not been fully characterized. Here we show that chaperone-mediated autophagy (CMA)5, a selective form of lysosomal protein degradation, is involved in sustaining HSC function in adult mice. CMA is required for protein quality control in stem cells and for the upregulation of fatty acid metabolism upon HSC activation. We find that CMA activity in HSCs decreases with age and show that genetic or pharmacological activation of CMA can restore the functionality of old mouse and human HSCs. Together, our findings provide mechanistic insights into a role for CMA in sustaining quality control, appropriate energetics and overall long-term HSC function. Our work suggests that CMA may be a promising therapeutic target for enhancing HSC function in conditions such as ageing or stem-cell transplantation.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-03129-z Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:591:y:2021:i:7848:d:10.1038_s41586-020-03129-z

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-03129-z

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().