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Status |
Public on Dec 28, 2023 |
Title |
TTP overexpression inhibits reconstitution potential of HSC but generates a dominant mitigating effect in collagen antibody-induced arthritis mice models |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Tristetraprolin (TTP), encoded by Zfp36 in mice, is one of the best characterized tandem zinc-finger mRNA binding protein involved in mRNA deadenylation and decay. TTPΔARE mice lack an AU-rich motif in the 3’ untranslated regions of TTP mRNA leading to increased TTP mRNA stability and more TTP protein, resulting in elevated mRNA decay rates of TTP targets. We examined the effect of TTP overexpression on the hematopoietic system and found alterations in red blood cell and white blood cell frequencies, with loss of platelets and B220 cells and gains of eosinophils and T-cells. TTPΔARE mice also have skewed primitive populations in the bone marrow with increases in myeloid-biased HSCs, but loss of granulocyte/macrophage biased MPP3 in both young and mid-aged mice. These populations changes were associated with cell-specific transcriptional alterations, but surprisingly consistent upregulation of TNF and TGFB signaling pathways in both progenitor populations. HSCs with overexpression of TTP had decreased reconstitution potential but generate hematopoietic environments that mitigate the inflammatory response induced by collagen antibody-induced arthritis (CAIA) model- even when TTP overexpressing cells are present at low frequencies. We present an overall analysis of elevated TTP expression in the early hematopoietic compartments which drives reduced overall reconstitution potential of the HSCs but leads to a dominant repression of inflammation induced in a rheumatoid arthritis model.
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Overall design |
Comparative gene expression profiling analysis of RNA-seq data for hematopetic stem cells (HSCs) and TPPdeltaARE HSCs
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Contributor(s) |
Tanaka-Yano M, Zong L, Park B, Beerman I |
Citation(s) |
37535204 |
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Submission date |
Feb 28, 2023 |
Last update date |
Mar 28, 2024 |
Contact name |
Bongsoo Park |
E-mail(s) |
[email protected]
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Phone |
1-410-558-8510
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Organization name |
National Institute on Aging
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Department |
Translational Gerontology Branch
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Lab |
Epigenetics and Stem Cell Aging
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Street address |
251 Bayview Blvd
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City |
Baltimore |
State/province |
Maryland |
ZIP/Postal code |
21224 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (24)
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Relations |
BioProject |
PRJNA939718 |