Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE158162 | GEO | 2021/02/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [ATAC-seq]

Project description:ATAC-seq analysis of wild type and Kmt2c mutant hematopoietic progenitors

2021-02-18 | GSE158158 | GEO

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [RNA-seq]

Project description:Rna-seq analysis of wild type and Kmt2c mutant hematopoietic progenitors

2021-02-18 | GSE158160 | GEO

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [ChIP-seq]

Project description:ChIP-seq analysis of wild type and Kmt2c mutant hematopoietic progenitors

2021-02-18 | GSE158159 | GEO

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy

Project description:Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy

| PRJNA664131 | ENA

Kmt2c mutations enhance HSC self-renewal capacity and convey a selective advantage after chemotherapy.

Project description:The myeloid tumor suppressor KMT2C is recurrently deleted in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly therapy-related MDS/AML (t-MDS/t-AML), as part of larger chromosome 7 deletions. Here, we show that KMT2C deletions convey a selective advantage to hematopoietic stem cells (HSCs) after chemotherapy treatment that may precipitate t-MDS/t-AML. Kmt2c deletions markedly enhance murine HSC self-renewal capacity without altering proliferation rates. Haploid Kmt2c deletions convey a selective advantage only when HSCs are driven into cycle by a strong proliferative stimulus, such as chemotherapy. Cycling Kmt2c-deficient HSCs fail to differentiate appropriately, particularly in response to interleukin-1. Kmt2c deletions mitigate histone methylation/acetylation changes that accrue as HSCs cycle after chemotherapy, and they impair enhancer recruitment during HSC differentiation. These findings help explain why Kmt2c deletions are more common in t-MDS/t-AML than in de novo AML or clonal hematopoiesis: they selectively protect cycling HSCs from differentiation without inducing HSC proliferation themselves.

| S-EPMC7951951 | biostudies-literature

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [ATAC-seq]

Project description:Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [ATAC-seq]

| PRJNA664184 | ENA

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [ChIP-seq]

Project description:Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [ChIP-seq]

| PRJNA664185 | ENA

Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [RNA-seq]

Project description:Kmt2c-mutations superimpose properties of activated and quiescent HSCs to convey a selective advantage after chemotherapy [RNA-seq]

| PRJNA664186 | ENA

Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent.

Project description:Hematopoietic stem cell (HSC)-based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein-displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34+ (hCD34+) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34+ cells, whereas conventional vesicular stomatitis virus G (VSV-G)-LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor. Importantly, reconstitution of NOD/SCIDγc-/- (NSG) mice with H/F-LV transduced prestimulated or resting hCD34+ cells confirmed these high transduction levels in all myeloid and lymphoid lineages. Remarkably, for resting CD34+ cells, secondary recipients exhibited increasing transduction levels of up to 100%, emphasizing that H/F-LVs efficiently gene-marked HSCs in the resting state. Because H/F-LVs promoted ex vivo gene modification of minimally manipulated CD34+ progenitors that maintained stemness, we assessed their applicability in Fanconi anemia, a bone marrow (BM) failure with chromosomal fragility. Notably, only H/F-LVs efficiently gene-corrected minimally stimulated hCD34+ cells in unfractionated BM from these patients. These H/F-LVs improved HSC gene delivery in the absence of cytokine stimulation while maintaining their stem cell potential. Thus, H/F-LVs will facilitate future clinical applications requiring HSC gene modification, including BM failure syndromes, for which treatment has been very challenging up to now.

| S-EPMC5728281 | biostudies-literature

The orphan nuclear receptor NR4A1 specifies a distinct subpopulation of quiescent myeloid-biased long-term HSCs.

Project description:Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1(GFP) BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin(-) Sca-1(+) c-Kit(+) CD48(-) CD150(+) long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1(GFP+) and NR4A1(GFP-) HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1(GFP+) HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs.

| S-EPMC4270858 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data