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Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases

ABSTRACT: Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases

PROVIDER: PRJNA553194 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9652770.fastq.gz	Fastqsanger.gz
	SRR9652761.fastq.gz	Fastqsanger.gz
	SRR9652771.fastq.gz	Fastqsanger.gz
	SRR9652762.fastq.gz	Fastqsanger.gz
	SRR9652763.fastq.gz	Fastqsanger.gz

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Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases

Project description:Although bone marrow (BM) niche cells are essential for hematopoietic stem cell (HSC) maintenance, their interaction in response to stress is not well defined. Here, we used a mouse model of acute thrombocytopenia to investigate the crosstalk between HSCs and niche cells during restoration of the thrombocyte pool. This process required membrane-localized stem cell factor (m-SCF) in megakaryocytes, which was regulated by vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor-B (PDGF-B) derived from BM endothelial cells. HSCs and multipotent progenitors 2 (MPP2), but not MPP3/4 were subsequently activated by a dual receptor tyrosine kinase (RTK)-dependent signaling event, namely m-SCF/c-Kit and VEGF-A/VEGFR-2, contributing to their selective and early proliferation. Our findings describe a dynamic network of signals in response to the acute loss of a single blood cell type, and reveal the important role of three RTKs in orchestrating the selective activation of HSCs and progenitor cells in thrombocytopenia.

2019-07-09 | GSE133947 | GEO

Profiling uterine fibroid specimens with an in-house array representing all 90 human tyrosine kinases and their ligands

Project description:The aim of this study is to compare the expression patterns of tyrosine kinases and their ligand activators between matched myometrium and leiomyoma tissues. For this, total RNA samples extracted from 42 pairs of matched fibroid and adjacent myometrial tissues were hybridized to a set of 840 customized oligonucleotide microarrays to compare the expression profiles of 244 selected human genes including all 90 tyrosine kinases and 103 ligands. Among the 244 genes surveyed, 38 were found to be differentially expressed between pairs of myometrium and fibroid tissues. Clustering analysis of the expression ratios of these 38 genes from 42 pairs of samples has led to the subdivision of fibroid samples into three groups, based on the expression ratios of two peptide ligands, CYR61 and EFNA4. Real-time quantitative RT-PCR measurements of additional 32 pairs of samples further confirmed the existence of these three groups of fibroid samples. In conclusion, peptide ligand activators of protein tyrosine kinases are differentially expressed between myometrium and fibroid tissues. This finding supports the notion that tyrosine kinases may be exploited as medical targets to treat symptomatic fibroids without surgical intervention.Â Â This study has been accomplished with 42 patients fibroid specimen and their matched myometrium, each pair of specimen has been repeated at least 3 times.

2009-11-20 | E-GEOD-19127 | biostudies-arrayexpress

Profiling uterine fibroid specimens with an in-house array representing all 90 human tyrosine kinases and their ligands

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Downregulation of RING ligase praja2 boosts receptor tyrosine kinases in kidney cancer

Project description:Downregulation of RING ligase praja2 boosts receptor tyrosine kinases in kidney cancer

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Untreated 32Dcl3 cell lines expressing oncogenic tyrosine kinases or cells treated with small molecule inhibitors

Project description:Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF-beta-R and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways. To identify the critical target genes required for transformation in hematopoietic cells, we used a comparative gene expression strategy in which selective small molecules were applied to 32Dcl3 cells that had been transformed to factor-independent growth by these respective oncogenic alleles. Keywords: comparative gene expression analysis

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