Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

B-myb is Essential Regulator of Hematopoietic Stem Cell and Myeloid Progenitor Cell Development

ABSTRACT: The B-myb (MYBL2) gene is a member of the MYB family of transcription factors and is involved in cell cycle regulation, DNA replication and maintenance of genomic integrity. However, its function during adult development and hematopoiesis is unknown. We show here that conditional inactivation of B-myb in vivo results in depletion of the HSC pool, leading to profound reductions in mature lymphoid, erythroid and myeloid cells. This defect is autonomous to the bone marrow and is first evident in the HSCs, which accumulate in the S and G2/M phases. B-myb inactivation also causes defects in the myeloid progenitor compartment and results in an accumulation of GMPs. Microarray studies indicate that B-myb null LKS+ cells differentially express genes that direct myeloid lineage development and commitment, suggesting that B-myb is a key player in controlling cell fate. Collectively, these studies demonstrate that B-myb is essential for HSC and progenitor maintenance and survival during hematopoiesis. Total RNA was isolated from FACS purified LKS+ cells isolated from pIpC-treated control and B-myb floxed-MxCre mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE53875 | GEO | 2014/02/12

SECONDARY ACCESSION(S): PRJNA233615

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

B-myb is Essential Regulator of Hematopoietic Stem Cell and Myeloid Progenitor Cell Development

Project description:The B-myb (MYBL2) gene is a member of the MYB family of transcription factors and is involved in cell cycle regulation, DNA replication and maintenance of genomic integrity. However, its function during adult development and hematopoiesis is unknown. We show here that conditional inactivation of B-myb in vivo results in depletion of the HSC pool, leading to profound reductions in mature lymphoid, erythroid and myeloid cells. This defect is autonomous to the bone marrow and is first evident in the HSCs, which accumulate in the S and G2/M phases. B-myb inactivation also causes defects in the myeloid progenitor compartment and results in an accumulation of GMPs. Microarray studies indicate that B-myb null LKS+ cells differentially express genes that direct myeloid lineage development and commitment, suggesting that B-myb is a key player in controlling cell fate. Collectively, these studies demonstrate that B-myb is essential for HSC and progenitor maintenance and survival during hematopoiesis. Total RNA was isolated from FACS purified LKS+ cells isolated from pIpC-treated control and B-myb floxed-MxCre mice. Each sample is derived from a pool of 3-5 mice. 2 samples were analyzed for each genotype.

2014-02-12 | E-GEOD-53875 | biostudies-arrayexpress

Cell of origin epigenetic priming determines susceptibility to Tet2 mutation

Project description:Hematopoietic stem cell (HSC) mutations can result in clonal hematopoiesis (CH) with heterogeneous clinical outcomes. Here, we investigated how the cell state preceding Tet2 mutation impacts the pre-malignant phenotype. Using an inducible system for clonal analysis of myeloid progenitors, we found that the epigenetic features of clones at similar differentiation status were highly heterogeneous and functionally responded differently to Tet2 mutation. Cell differentiation stage also influenced Tet2 mutation response indicating that the cell of origin's epigenome modulates clone-specific behaviors in CH. Molecular features associated with higher risk outcomes include Sox4 that sensitized cells to Tet2 inactivation, inducing dedifferentiation, altered metabolism and increasing the in vivo clonal output of mutant cells, as confirmed in primary GMP and HSC models. Our findings validate the hypothesis that epigenetic features can predispose specific clones for dominance, explaining why identical genetic mutations can result in different phenotypes.

1970-01-01 | MTBLS9914 | MetaboLights

RNA-seq study on mouse bone marrow leukemia cells isolated from secondary transplant recipients receiving conditional knockout Arid1b or Arid2 MLL-AF9 cells

Project description:We isolated whole bone marrow leukemia cells from moribund secondary transplant recipients receiving VavCre+ (control), Arid1b fl/fl VavCre+ (knockout), Arid2 fl/fl VavCre+ (knockout), MxCre+ (control), Arid1b fl/fl MxCre+ (knockout), or Arid2 fl/fl MxCre+ (knockout) primary MLL-AF9 cells. Mice receiving MxCre+ (control), Arid1b fl/fl MxCre+ (knockout), or Arid2 fl/fl MxCre+ (knockout) MLL-AF9 cells were injected with pIpC 21 days post transplant. Total RNA was isolated followed by mRNA selection. cDNA libraries were generated and NextGen Sequencing was performed.

2022-03-08 | GSE188291 | GEO

Transcription profiling of mouse gain- and loss-of-function Hedgehod (Hh) genetic models reveals Hedgehog signaling is dispensable for adult hematopoietic stem cell function

Project description:The Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or over-activation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as RBPJ- and Smo-deficiency do not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression âsignatureâ. Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that the Hh pathway can be targeted in future clinical trials addressing the effect of Hh inhibition on leukemia-initiating cell maintenance. Transcriptional consequences of inactivating Smo (hh loss-of-function) in LKS cells. Experiment Overall Design: Four samples were analyzed: wild-type (WT) control and Smo-deficient (SMO) Lin-ckit+Sca1+ (LSK) cells, as well as Lin-ckit+Sca1- myeloid progenitor (MP) cells, which served as a control for LSK-enriched/specific genes. Total bone marrow cells were pooled from four WT and four SMO mice before sorting LSK and MP populations.

2009-03-21 | E-GEOD-15194 | biostudies-arrayexpress

MYB is an essential regulator of primitive human hematopoiesis in human pluripotent stem cell differentiation cultures.

Project description:MYB is well recognized to be a key regulator of definitive hematopoiesis that plays an important role in the maintenance and multilineage differentiation of hematopoietic stem cells (HSCs). In the vertebrate developmental context, MYB is widely regarded dispensable for primitive hematopoiesis but critically required for the development of definitive hematopoiesis. To explore the role of MYB in human hematopoietic development we have inactivated the gene by bi-allelic TALEN-supported gene targeting in several lines of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), and subjected these cells to hematopoietic differentiation in well-defined cell culture conditions. Venus gene reporter was inserted into the knock-in allele to monitor MYB expression during the course of the hESC/iPSC differentiation. The gene reporter system showed that MYB is specifically expressed during hematopoietic commitment in the earliest primitive blood cells. Moreover, the level of MYB expression was highest at the commitment stage of differentiation and significantly decreased at the maturations stage. We found that MYB was not required for initial hematopoietic commitment of nascent mesoderm and emergence of primitive, yolk sac-type human hematopoietic progenitors. However, inactivation of MYB severely abrogated proliferation of the primitive erythroid and mixed erythroid-macrophage-megakaryocyte progenitors. In addition, MYB-negative hESC/iPSC lines demonstrated major defects in myeloid cell development and completely failed to generate mature granulocytes. Transposon-mediated rescue of MYB expression in MYB-null cells efficiently restored both the primitive hematopoietic progenitors and immature myeloid cells. Our data indicate that in contrast to its previously attributed exclusive role in definitive hematopoiesis, MYB is indispensable for primitive human hematopoiesis.

2021-01-31 | GSE125761 | GEO

RNA-seq study on mouse bone marrow HSPC cells isolated from Arid2 conditional knockout and control mice.

Project description:We isolated lineage negative, cKit+, Sca1+ hematopoietic stem and progenitor cells from mouse bone marrow from Arid2fl/fl:MxCre+ (knockout) and MxCre+ (control) mice. Mice were injected with pIpC 6 weeks prior to isolation of LSK cells. Total RNA was isolated followed by mRNA selection. cDNA libraries were generated and NextGen Sequencing was performed.

2021-01-08 | GSE164384 | GEO

Effect of loss of Gfi1b on hematopietic stem cells

Project description:Using Gfi1b conditional mice, deletion of gfi1b in the hematopietic system was induced by injecting MxCre tg Gfi1bfl/fl mice with pIpC. 30 days after injection, Cd150 pos, Cd 48 neg, Lin neg Sca and c-kit pos stem cells were sortrted from Gfi1bfl/fl and Mxcre tg Gfi1bfl/fl mice and analysed. We used the mouse Affymetrix Gene ST Array.

2010-09-03 | GSE20655 | GEO

Gene-expression changes resulting from loss of the mTORC1 component Raptor in murine hematopoietic stem and progenitor cell-enriched populations (HSPC)

Project description:We investigated the role of mTORC1 in murine hematopoiesis by conditionally deleting the Raptor gene in murine hematopoietic stem cells. We observed mutliple alterations evoked by Raptor loss in hematopoiesis and profiled gene-expression alterations induced by raptor loss in Flt3-Lin-Sca1+cKit+ hematopoietic stem and progenitor enriched cell populations, 5 weeks post Raptor deletion. Flt3-Lin-Sca1+cKit+ cells were flow sorted from mice containing homozygous floxed alleles for exon 6 of the Raptor gene in the presence (MT group) or absence (WT group) of the MxCre transgene, which was induced with injections of mice with pIpC 5 weeks before cell isolation.

2012-09-19 | E-GEOD-32265 | biostudies-arrayexpress

Gene expression data from long term hematopoietic stem cells (LT-HSC, Lin-Sca-1+c-kit+CD34-CD135-) isolated from control, MxCre Jak2VF/+ and MxCre Jak2VF/+ EZH2-/- mice

Project description:Inactivating EZH2 mutations have been associated with myelofibrosis (MF). Moreover, EZH2 mutations co-exist with the JAK2V617F mutation in a significant cases of MF. To determine the effects of concomitant loss of EZH2 and JAK2V617F mutation in hematopoiesis, we generated Ezh2-deficient Jak2V617F-expressing mice. To gain insights into the mechanisms by which Ezh2 deficiency promotes the development of MF in Jak2V617F knock-in mice, we performed microarray gene expression analysis on sorted LT-HSC from control, MxCre;Jak2VF/+ and MxCre;Jak2VF/+ EZH2-/- mice.

2016-04-19 | GSE79198 | GEO

Transcription profiling of mouse long term HSC from control or Pbx1-null mice

Project description:Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. A significant proportion of Pbx1-dependent genes are associated with the Tgf-b pathway, which serves a major role in maintaining HSC quiescence. Pbx1-deficient LT-HSCs are unable to up-regulate the cyclin dependent kinase inhibitor p57 in response to Tgf-b, providing a mechanism through which Pbx1 maintenance of stem cell self-renewal is achieved. Experiment Overall Design: Highly efficient Pbx1 deletion was induced with poly(I:C) in 3 young MxCre+.Pbx1f/f mutant or 2 MxCre-.Pbx1f/f control mice. LT-HSC (Lin-cKit+Sca1+CD34-CD135-) cells were prospectively sorted from bone marrow of individual mice harvested 4 weeks after the last injection of poly(I:C).

2008-06-20 | E-GEOD-9188 | biostudies-arrayexpress

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