Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nuclear myosin 1 regulates platelet activation and immune response in mice

ABSTRACT: Cellular differentiation involves a complex series of events associated with changes in cellular shape, function, and proliferative capacity. This process is mostly regulated by specific expression of multiple genes which guide the cell through the differentiation process but also ensure proper function of terminal cell types. Over the last decade, the role of cellular metabolism in maintaining the pluripotency of stem cells and subsequent differentiation is getting more attention as there is a direct link between the metabolic status of cells and their differentiation potential. We have recently shown that deletion of Nuclear Myosin 1 (NM1) leads to a molecular switch from oxidative phosphorylation to glycolysis and subsequent tumorigenesis in mice. Here we performed an in vitro analysis of metabolomic profiles associated with NM1 loss and measured the cytokine and chemokine levels in cells to provide evidence for a possible role of NM1 during hematopoiesis. Moreover, we explored the role of NM1 during the differentiation of hematopoietic progenitor stem cells to terminal blood cells by transcriptomic analysis of bone marrow, spleen, and peripheral blood. We found that in bone marrow, NM1 deletion leads to overexpression of genes associated with glycolysis-dependent platelet activation and suppression of the innate immune system genes. Remarkably, these expression patterns are preserved and become more complex in the spleen and peripheral blood. The study therefore provides novel insights into the underlying mechanisms of hematopoietic differentiation and activation of specific blood cell types and suggests NM1 as a potential therapeutic target for blood-related disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE293993 | GEO | 2026/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Nuclear myosin 1 regulates platelet activation and immune response in mice

Project description:Here we suggest that NM1 regulation of oxidative phosphorylation in mitochondria has an effect on hematopoietic progenitor stem cells during their differentiation to terminal blood and bone marrow stromal cells. Deletion of NM1 in the bone marrow tissue leads to differential gene expression associated with platelet activation and blood coagulation; immune system response and osteoclast differentiation. The platelet activation gene programs which are dependent on glycolysis are upregulated in NM1 KO tissue, while lymphocyte and osteoclast differentiation which is dependent on oxidative phosphorylation is suppressed in NM1 KO bone marrow.

2023-02-28 | GSE224167 | GEO

Nuclear Myosin 1 depletion leads to a metabolic reprogramming of cells and tumorigenesis in mice

Project description:Metabolic reprograming is one of the hallmarks of tumorigenesis. Using a combination of multi-omics, here we show that nuclear myosin 1 (NM1) serves a key regulator of cellular metabolism. As part of nutrient-sensing PI3K/Akt/mTOR pathway, NM1 forms a positive feedback loop with mTOR, and directly affects mitochondrial oxidative phosphorylation via transcriptional regulation of mitochondrial transcription factors TFAM and PGC1α. NM1 depletion leads to a suppression of PI3K/Akt/mTOR pathway, underdevelopment of mitochondria inner cristae and redistribution of mitochondria within a cell, which is associated with reduced expression of oxidative phosphorylation genes, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics. This leads to a metabolic reprogramming of NM1 KO cells from oxidative phosphorylation to aerobic glycolysis and with that associated metabolomic profile typical for cancer cells, namely, increased amino acid-, fatty acid-, and sugar metabolism, and increase in glucose uptake, lactate production and intracellular acidity. We show that NM1 KO cells are able to form solid tumors in a nude mouse model even though they have supressed PI3K/Akt/mTOR signalling pathway suggesting that the metabolic switch towards aerobic glycolysis provide a sufficient signal for carcinogenesis. We suggest that NM1 plays a key role as tumor suppressor and that NM1 depletion may be partly responsible for the Warburg effect at the early onset of tumorigenesis.

2022-06-27 | GSE206858 | GEO

Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice

2023-07-13 | GSE236679 | GEO

The niche for extramedullar hematopoiesis in the spleen

Project description:Adult hematopoietic stem cells (HSCs) reside primarily in bone marrow. However, hematopoietic stresses such as myelofibrosis, anemia, pregnancy, infection or myeloablation can mobilize HSCs to the spleen and induce extramedullary hematopoiesis (EMH). While the bone marrow HSC niche has been studied intensively, the EMH niche has received little attention. Here, we systematically assessed the physiological sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by cyclophosphamide plus granulocyte colony-stimulating factor, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow hematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create the splenic EMH niche, which is necessary for the physiological response to diverse hematopoietic stresses. Unfractionated spleen cells (2 replicates) and FACS-sorted VE-cadherein negative Scf-GFP positive cells (3 replicates)

2015-08-01 | E-GEOD-71288 | biostudies-arrayexpress

The niche for extramedullar hematopoiesis in the spleen

2015-08-01 | GSE71288 | GEO

Igf2bp2 deletion reduces energy metabolism, gIgf2bp2 deletion reduces energy metabolism, growth signaling, and aging of hematopoietic stem cells in micerowth signaling, and aging of hematopoietic stem cells in mice

Project description:Increasing evidence links metabolic activity and cell growth to decline in hematopoietic stem cell (HSC) function during aging. The Lin28b/Hmga2 pathway controls tissue development and in the hematopoietic system the postnatal downregulation of this pathway causes a decrease in self renewal of adult HSCs compared to fetal HSCs. Igf2bp2 is an RNA binding protein and a mediator of the Lin28b/Hmga2 pathway, which regulates metabolism and growth signaling by influencing RNA stability and translation of its target genes. It is currently unknown whether Lin28/Hmga2/Igf2bp2 signaling impacts on aging-associated impairments in HSC function and hematopoiesis. Here, we analyzed homozygous Igf2bp2 germline knockout mice and wildtype control animals to address this question. The study shows that Igf2bp2 deletion rescues aging phenotypes of the hematopoietic system, such as the expansion of HSC numbers in bone marrow and the biased increase of myeloid cells in peripheral blood. This rescue of hematopoietic aging coincides with reduced mitochondrial metabolism and glycolysis in Igf2bp2-/- HSCs compared to Igf2bp2+/+ HSCs. Conversely, Igf2bp2 overexpression activates protein synthesis pathways in HSCs and leads to a rapid loss of self renewal by enhancing myeloid skewed differentiation in an mTOR/PI3K-dependent manner. Together, these results show that Igf2bp2 regulates energy metabolism and growth signaling in HSCs and that the activity of this pathways influences self renewal, differentiation, and aging of HSCs.

2024-05-21 | PXD018535 | Pride

A Congenital Anemia Dissociates the Pleiotropic Functions of Master Transcription Factor GATA1 [Patient_RNAseq]

Project description:Master regulators, such as the hematopoietic transcription factor GATA1, have numerous roles in lineage commitment and differentiation. While human GATA1 mutations result in several blood diseases, all characterized mutations act relatively early to impair hematopoietic differentiation. Here, we describe a distinct form of hemolytic anemia involving impaired terminal erythropoiesis with a reduced lifespan of circulating red blood cells. We show that this unique blood disorder results from mutations in a poorly characterized and intrinsically disordered C-terminal region of GATA1.

2021-12-31 | GSE133414 | GEO