PXD022196

PXD022196 is an original dataset announced via ProteomeXchange.

Title	Chaperone-mediated autophagy sustains hematopoietic stem cell function
Description	Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production1, 2. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division3-8. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a role for chaperone-mediated autophagy (CMA)9, a selective form of lysosomal protein degradation, in sustaining adult HSC function. CMA is required for stem cell protein quality control and upregulation of fatty acid metabolism upon HSC activation. We identify that CMA activity decreases with age in HSC and show that genetic or pharmacological activation of CMA can restore functionality of old HSC. Together, our findings provide mechanistic insights into a new role for CMA in sustaining quality control, appropriate energetics and overall long-term hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation.
HostingRepository	PRIDE
AnnounceDate	2021-03-05
AnnouncementXML	Submission_2021-03-04_22:41:32.175.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022196
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Monika Dzieciatkowska
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monoacetylated residue; Pyro-carbamidomethyl; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-27 01:30:45	ID requested
⏵ 1	2021-03-04 22:41:33	announced

Dong S, Wang Q, Kao YR, Diaz A, Tasset I, Kaushik S, Thiruthuvanathan V, Zintiridou A, Nieves E, Dzieciatkowska M, Reisz JA, Gavathiotis E, D'Alessandro A, Will B, Cuervo AM, Chaperone-mediated autophagy sustains haematopoietic stem-cell function. Nature, 591(7848):117-123(2021) [pubmed]

submitter keyword: autophagy

chaperones

lipid metabolism

lysosomes

protein degradation

protein quality control

stem cells

Ana Maria Cuervo
contact affiliation	The Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases Professor Department of Developmental and Molecular Biology Co-director Institute for Aging Research Albert Einstein College of Medicine
contact email	ana-maria.cuervo@einsteinmed.org
lab head
Monika Dzieciatkowska
contact affiliation	UC Denver
contact email	monika.dzieciatkowska@ucdenver.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD022196

PRIDE project URI

• PRIDE
  1. PXD022196
     1. Label: PRIDE project
     2. Name: Chaperone-mediated autophagy sustains hematopoietic stem cell function