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Status |
Public on Jul 09, 2019 |
Title |
Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
Examination of hematopoietic stem cells CD41+ vs. CD41- from control mice and 24h after platelet depletion, biological replicates (cells from 3 mice per sample)
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Contributor(s) |
Ramasz B, Krüger A, Reinhardt J, Sinha A, Gerlach M, Gerbaulet A, Reinhardt S, Dahl A, Chavakis T, Wielockx B, Grinenko T |
Citation(s) |
31434705 |
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Submission date |
Jul 08, 2019 |
Last update date |
Feb 09, 2022 |
Contact name |
Ben Wielockx |
E-mail(s) |
ben.wielockx@tu-dresden.de
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Organization name |
IKL, Carl Gustav Carus Universitätklinikum Dresden
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Street address |
Fetscherstrasse 74
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City |
Dresden |
ZIP/Postal code |
01307 |
Country |
Germany |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (11)
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Relations |
BioProject |
PRJNA553194 |
SRA |
SRP213641 |