PXD011537-2

PXD011537 is an original dataset announced via ProteomeXchange.

Title	Rad21-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation
Description	MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
HostingRepository	PRIDE
AnnounceDate	2018-12-04
AnnouncementXML	Submission_2018-12-04_04:08:05.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joanna Kirkpatrick
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	2018-10-31 07:37:11	ID requested
1	2018-11-28 02:56:42	announced
⏵ 2	2018-12-04 04:08:06	announced	Updated project metadata.
3	2018-12-13 00:50:07	announced	Updated project metadata.
4	2018-12-21 01:29:46	announced	Updated project metadata.

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: Aging, inflammation, hematopoietic stems cells

Karl Lenhard Rudolph
contact affiliation	Research Group on Stem Cell Aging Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) Beutenbergstraße 11 07745 Jena, Germany
contact email	Lenhard.Rudolph@leibniz-fli.de
lab head
Joanna Kirkpatrick
contact affiliation	Leibniz Institute on Aging - FLI
contact email	joanna.kirkpatrick@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/2018/11/PXD011537

PRIDE project URI

• PRIDE
  1. PXD011537
     1. Label: PRIDE project
     2. Name: Rad21-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation