PXD018535

PXD018535 is an original dataset announced via ProteomeXchange.

Title	Igf2bp2 deletion reduces energy metabolism, gIgf2bp2 deletion reduces energy metabolism, growth signaling, and aging of hematopoietic stem cells in micerowth signaling, and aging of hematopoietic stem cells in mice
Description	Increasing evidence links metabolic activity and cell growth to decline in hematopoietic stem cell (HSC) function during aging. The Lin28b/Hmga2 pathway controls tissue development and in the hematopoietic system the postnatal downregulation of this pathway causes a decrease in self renewal of adult HSCs compared to fetal HSCs. Igf2bp2 is an RNA binding protein and a mediator of the Lin28b/Hmga2 pathway, which regulates metabolism and growth signaling by influencing RNA stability and translation of its target genes. It is currently unknown whether Lin28/Hmga2/Igf2bp2 signaling impacts on aging-associated impairments in HSC function and hematopoiesis. Here, we analyzed homozygous Igf2bp2 germline knockout mice and wildtype control animals to address this question. The study shows that Igf2bp2 deletion rescues aging phenotypes of the hematopoietic system, such as the expansion of HSC numbers in bone marrow and the biased increase of myeloid cells in peripheral blood. This rescue of hematopoietic aging coincides with reduced mitochondrial metabolism and glycolysis in Igf2bp2-/- HSCs compared to Igf2bp2+/+ HSCs. Conversely, Igf2bp2 overexpression activates protein synthesis pathways in HSCs and leads to a rapid loss of self renewal by enhancing myeloid skewed differentiation in an mTOR/PI3K-dependent manner. Together, these results show that Igf2bp2 regulates energy metabolism and growth signaling in HSCs and that the activity of this pathways influences self renewal, differentiation, and aging of HSCs.
HostingRepository	PRIDE
AnnounceDate	2024-05-21
AnnouncementXML	Submission_2024-05-21_12:13:58.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erika Kelmer Sacramento
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-14 03:26:40	ID requested
⏵ 1	2024-05-21 12:13:59	announced

Suo M, Rommelfanger MK, Chen Y, Amro EM, Han B, Chen Z, Szafranski K, Chakkarappan SR, Boehm BO, MacLean AL, Rudolph KL, Age-dependent effects of Igf2bp2 on gene regulation, function, and aging of hematopoietic stem cells in mice. Blood, 139(17):2653-2665(2022) [pubmed]

10.1182/blood.2021012197;

submitter keyword: mitochondrial metabolism, protein synthesis and mTOR/PI3K-dependent differentiation of hematopoietic stem cells.,Igf2bp2 drives glycolysis

K. Lenhard Rudolph
contact affiliation	Leibniz Institute on Aging, Fritz Lipmann Institute (FLI)
contact email	Lenhard.Rudolph@Leibniz-Fli.de
lab head
Erika Kelmer Sacramento
contact affiliation	Leibniz Institute on Aging - Fritz Lipmann Institute
contact email	erika.kelmer@leibniz-fli.de
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/2024/05/PXD018535

PRIDE project URI

• PRIDE
  1. PXD018535
     1. Label: PRIDE project
     2. Name: Igf2bp2 deletion reduces energy metabolism, gIgf2bp2 deletion reduces energy metabolism, growth signaling, and aging of hematopoietic stem cells in micerowth signaling, and aging of hematopoietic stem cells in mice