Myh9 plays essential role in hematopoietic stem/progenitor cells survival and maintenance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA813848 | ENA |
REPOSITORIES: ENA
Dataset's files
| 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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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
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. Our present study suggests an essential role for Myh9 in the survival and maintenance of HSPC in normal hematopoiesis.
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Project description:Non-muscle myosin IIA plays an important role in cell adhesion, cell migration and tissue architecture. We previously showed that low activity of the heavy chain of non-muscle myosin II Myh9 is beneficial to Lgr5+ intestinal stem cell maintenance. However, the function of Myh9 in adult mouse intestinal epithelium is largely unclear. In this study, we used the inducible Villin-creERT2 knockout approach to delete Myh9 in adult mouse intestinal epithelium and observed that homozygous deletion of Myh9 causes colitis-like morphologic changes in intestine, leads to a high sensitivity to dextran sulfate sodium and promotes the colitis related adenomas formation in colon. Myh9 deletion disturbs cell junctions and impairs intestinal lumen barrier integrity, promoting the necroptosis of epithelial cells. Consistently, these changes can be partially rescued by Ripk3 knockout. Our results indicate that Myh9 is required for the maintenance of intestinal epithelium integrity and the prevention of cell necroptosis.
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Project description:Myh9 knockdown reduces the strength of the apical actomyosin cortex from hepatocytes, which causes isotropic growth of the bile canaliculus (BC) and ultimately results in the formation of hepatocyte cysts with a large central apical lumen. Treatment of hepatocytes with the osmotically active bioinert polymer PEG950 causes and increase in intraluminal pressure, which causes expansion of the bile canaliculus (BC) and ultimately results in the formation of hepatocyte cysts with a large central apical lumen. In these cysts, hepatocytes have common apico-basal polarity, such as observed for simple epithelia like cholangiocytes. To investigate whether this change in apical lumen morphology and polarization is associated with alterations in gene expression we compared hepatocytes with and without Myh9 knockdown and with and without PEG950 treatment.
2024-10-16 | GSE278503 | GEO
Project description:Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classical epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in hypertensive patients is important for investigating novel hypertension mechanisms.Differential genomic DNA methylation in hypertensive, prehypertensive, and healthy control individuals was screened using the Illumina 450K BeadChip and verified by pyrosequencing. Plasma oviduct glycoprotein 1 (OVGP1) levels were determined using an enzyme-linked immunosorbent assay. Ovgp1 transgenic and knockout mice were generated to analyze the function of OVGP1. The blood pressure levels of the mouse models were measured using the tail-cuff system and radiotelemetry methods. The role of OVGP1 in vascular remodeling was determined by vascular relaxation studies. Protein–protein interactions were investigated using a pull-down/mass spectrometry assay and verified with coimmunoprecipitation and pull-down assays. We found a hypomethylated site at cg20823859 in the promoter region of OVGP1, and the plasma OVGP1 levels were significantly increased in hypertensive patients. This finding indicates that OVGP1 is associated with hypertension. In Ovgp1 transgenic mice, OVGP1 overexpression caused an increase in blood pressure, dysfunctional vasoconstriction and vasodilatation, remodeling of arterial walls, and increased vascular superoxide stress and inflammation, and these phenomena were exacerbated by angiotensin II infusion. In contrast, Ovgp1 deficiency attenuated angiotensin II-induced vascular oxidase stress, inflammation, and collagen deposition. These findings indicate that OVGP1 is a prohypertensive factor that directly promotes vascular remodeling. Pull-down and coimmunoprecipitation assays showed that myosin heavy chain II-A (MYH9) interacted with OVGP1, whereas inhibition of MYH9 attenuated OVGP1-induced hypertension and vascular remodeling. CONCLUSIONS: Hypomethylation at cg20823859 in the promoter region of OVGP1 is associated with hypertension and induces upregulation of OVGP1. The interaction between OVGP1 and MYH9 contributes to vascular remodeling and dysfunction. Therefore, OVGP1 is a prohypertensive factor that promotes vascular remodeling by binding with MYH9.
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Project description:The regulation of stem cell survival, self-renewal, and differentiation is critical for the maintenance of tissue homeostasis. Although the involvement of signaling pathways and transcriptional control mechanisms in stem cell regulation have been extensively investigated, the role of post-transcriptional control is still poorly understood. Here we show that the nuclear activity of the RNA-binding protein Second Mitotic Wave Missing (Swm) is critical for Drosophila melanogaster intestinal stem cells (ISCs) and their daughter cells, enteroblasts (EBs), to maintain their progenitor cell properties and function. Loss of swm causes ISCs and EBs to stop dividing and instead detach from the basement membrane, resulting in severe progenitor cell loss. swm loss is furthermore characterized by nuclear accumulation of poly(A)+ RNA in progenitor cells. Swm associates with transcripts involved in epithelial cell maintenance and adhesion, and the loss of swm, while not generally affecting the levels of these Swm-bound mRNAs, leads to elevated expression of proteins encoded by some of them, including the fly ortholog of Filamin. Taken together, this study indicates a nuclear role for Swm in adult stem cell maintenance, raising the possibility that nuclear post-transcriptional gene regulation plays vital roles in controlling adult stem cell maintenance and function.
2022-06-25 | GSE206632 | GEO
Project description:Phosphatidylinositol 3-kinase (PI3K) signaling plays a central role in various biological processes, and its abnormality leads to a broad spectrum of human diseases, such as cancer, fibrosis, and immunological disorders. However, the mechanisms by which PI3K signaling regulates the behavior of stem cells during regeneration are poorly understood. Planarian flatworms possess abundant adult stem cells (called neoblasts) allowing them to develop remarkable regenerative capabilities, thus the animals represent an ideal model for studying stem cells and regenerative medicine in vivo. In this study, the spatiotemporal expression pattern of Djpi3k, a PI3K ortholog in the planarian Dugesia japonica, was investigated and suggests its potential role in wound response and tissue regeneration. A loss-of-function study was conducted using small molecules and RNA interference technique, providing evidence that PI3K signaling is required for blastema regrowth and cilia maintenance during planarian regeneration and homeostasis. Interestingly, the mitotic and apoptotic responses to amputation are substantially abated in PI3K inhibitor-treated regenerating animals, while knockdown of Djpi3k alleviates the mitotic response and postpones the peak of apoptotic cell death, which may contribute to the varying degrees of regenerative defects induced by the pharmacological and genetic approaches. These observations reveal novel roles for PI3K signaling in the regulation of the cellular responses to amputation during planarian regeneration and provide insights for investigating the disease-related genes in the regeneration-competent organism in vivo.
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Project description:Intestinal metaplasia (IM), precancerous lesions of gastric carcinoma (PLGC) induced by factors like nitrite, Helicobacter pylori, or bile acid, carries a high risk of progressing to gastric cancer. IM is categorized into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients with IIM are at a higher risk of developing gastric cancer, emphasizing its importance for early screening. Besides the diagnostic challenges, the mechanisms underlying its progression remain a mystery. OLFM4, a gene associated with stemness characteristics, has been linked to promoting gastric and colorectal cancers. Our investigation used pathological sections from two clinical centers, biopsies of IM tissues, PLGC cell models, animal models, and organoids to explore OLFM4's role in IIM. OLFM4 expression was observed highly in IIM, with superior diagnostic accuracy of IIM compared to CDX2 and MUC2 for the first time. OLFM4, along with MYH9, was highly expressed in IM organoids and PLGC animal models. OLFM4, in combination with MYH9, accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, finally promoting the proliferation and invasion abilities of PLGC cells. In conclusion, OLFM4 serves as a novel biomarker for IIM and is utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. This study provides new insights into the mechanisms of progression and a new target of therapy in intestinal metaplasia.
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2011-05-19 | E-GEOD-21480 | biostudies-arrayexpress