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Myh9 plays essential role in hematopoietic stem/progenitor cells survival and maintenance

ABSTRACT: Myh9 plays essential role in hematopoietic stem/progenitor cells survival and maintenance

PROVIDER: PRJNA813848 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18270958_1.fastq.gz	Fastqsanger.gz
	SRR18270958_2.fastq.gz	Fastqsanger.gz
	SRR18270959_1.fastq.gz	Fastqsanger.gz
	SRR18270959_2.fastq.gz	Fastqsanger.gz
	SRR18270960_1.fastq.gz	Fastqsanger.gz

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Myh9 plays essential role in hematopoietic stem/progenitor cells survival and maintenance

Project description:Myosin heavy chain 9 (MYH9) gene encodes a protein named non-muscle heavy chain IIA (NMHC IIA), interacting with actin and participating in various biological processes. Mutations in MYH9 cause an array of autosomal dominant disorders, known as MYH9-related diseases (MYH9-RD). However, the role of MYH9 in normal hematopoiesis remains largely unexplored. By using Mx1-cre Myh9 conditional knockout mice, we established an inducible system to precisely inactivate Myh9 function in hematopoietic cells in vivo. The results showed that deletion of Myh9 led to severe defects in hematopoiesis, characterized by pancytopenia, drastic decreases of hematopoietic stem/progenitor cells (HSPC), and bone marrow failure, causing early lethality in mice. The defect in hematopoiesis caused by Myh9 ablation is cell autonomous. In addition, Myh9 deletion impairs HSPC repopulation capacity and increases apoptosis. RNA sequencing results revealed significant alterations in the expression of genes related to HSC self-renewal and maintenance, while multiple signal pathways were also involved, including genes for HSC and myeloid cell development, intrinsic apoptosis, targets of mTOR signaling, and maturity of hematopoietic cells. Collectively, our findings suggest an essential role for Myh9 in the survival and maintenance of HSPC in normal hematopoiesis.

2022-06-01 | GSE198134 | GEO

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

Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells.

Project description:Src homology 2 domain-containing phosphatase 2 (Shp2), encoded by Ptpn11, is a member of the nonreceptor protein-tyrosine phosphatase family, and functions in cell survival, proliferation, migration, and differentiation in many tissues. Here we report that loss of Ptpn11 in murine hematopoietic cells leads to bone marrow aplasia and lethality. Mutant mice show rapid loss of hematopoietic stem cells (HSCs) and immature progenitors of all hematopoietic lineages in a gene dosage-dependent and cell-autonomous manner. Ptpn11-deficient HSCs and progenitors undergo apoptosis concomitant with increased Noxa expression. Mutant HSCs/progenitors also show defective Erk and Akt activation in response to stem cell factor and diminished thrombopoietin-evoked Erk activation. Activated Kras alleviates the Ptpn11 requirement for colony formation by progenitors and cytokine/growth factor responsiveness of HSCs, indicating that Ras is functionally downstream of Shp2 in these cells. Thus, Shp2 plays a critical role in controlling the survival and maintenance of HSCs and immature progenitors in vivo.

| S-EPMC3087477 | biostudies-other

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

2014-02-12 | GSE53875 | GEO

Epithelial EP4 plays an essential role in maintaining homeostasis in colon

Project description:Epithelial EP4 plays an essential role in maintaining homeostasis in colon

| PRJNA560350 | ENA

Regulation of mitophagy by O-linked N-acetylglucosamine transferase is essential for hematopoietic stem cell maintenance

Project description:O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes post-translational modification of target proteins by introducing O-GlcNAc moiety on serine or threonine residues. OGT critically regulates various cellular functions in many cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) are totally unknown. Here we report critical roles of OGT in homeostasis of HSPCs. Ogt is highly expressed in HSPCs and its disruption led to their rapid loss with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient HSCs lost quiescence and showed severe defects in self-renewal and long-term repopulation capacities. Interestingly, Ogt-deficient HSCs accumulated defective mitochondria due to impaired mitophagy with decreased key mitophagy regulators, Pink1 and Bnip3, through dysregulation of host cell factor 1 (HCF1)-H3K4me3 pathway, and overexpression of Pink1 rescued impaired mitophagy and numbers of Ogt-deficient HSCs. In summary, our results revealed that OGT plays an essential role in HSC maintenance by assuring mitochondrial quality through mitophagy.

2020-12-09 | GSE116433 | GEO

Repression of p53-target gene Bbc3/puma by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance

Project description:Repression of p53-target gene Bbc3/puma by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance

| PRJNA633124 | ENA

MLL2, but not MLL1, plays a major role to sustain leukemia survival

Project description:MLL2, but not MLL1, plays a major role to sustain leukemia survival

| PRJNA362633 | ENA

ß-catenin Plays a Dual Role in the Generation and Maintenance of Immortalized Hematopoietic Stem Cells

Project description:Hematopoietic stem cells (HSCs) are characterized by their ability to give rise to all mature blood lineages and to renew themselves. Despite their potential for the therapeutic use in cell replacement therapy, the cell fate decisions of HSCs controlled by extrinsic and intrinsic mechanisms remain poorly understood. In summary, our results provide a number of novel and important observations illustrating and enlightening the importance of ß-catenin in hematopoiesis. Specifically, we show that ß-catenin plays an essential role in the immortalization of HSCs. Keywords: hematopoietic stem cells , immortalization, ß-catenin, genetic modification, time course

2006-12-06 | GSE6424 | GEO