Tgif1 regulates quiescence and self-renewal signaling pathways of hematopoietic stem cells (HSCs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Yan Guo
PROVIDER: E-GEOD-50739 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:In this study we demonstrate that Tgif1 has a role in HSCs maintenance, self-renewal and quiescence. RNA sequencing data of LSK cells (HSCs enriched cell population) from Tgif1-/- and wild type mice implicates that multiple pathways involved in HSC quiescence and self-renewal are disturbed in Tgif1 deficient mice.
2013-09-10 | GSE50739 | GEO
Project description:Tgif1 regulates quiescence and self-renewal signaling pathways of hematopoietic stem cells (HSCs)
| PRJNA218619 | ENA
Project description:Hematopoietic stem cells (HSCs) are capable of both self-renewing throughout the lifetime of an organism and differentiating into all lineages of the blood system. A proper balance between quiescence and proliferation is critical for the self-renewal and functions of HSCs. To identify the functions of the slicer endonuclease Argonaute (Ago) 2 in the physiology of HSCs, we generated Ago2Hem-KO mice, that are deficient for Ago2 in HSCs and in their progeny. Our analysis indicated that Ago2 deficient HSCs show increased quiescence and reduced entry to proliferation. To understand molecular mechanisms that are deregulated in Ago2 deficient hematopoietic stem and progenitor cells (HSPCs), we isolated Lin-Sca1+c-Kit+ (LSK) cells from control and Ago2 deficient mice and performed microarray analysis using the Illumina's MouseWG-6 v2.0 Expression BeadChip platform.
2015-11-13 | GSE74946 | GEO
Project description:Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others. 12 RNA samples from mouse bone marrows were analyzed. There are three biological replicates for each subtype.
2014-03-14 | E-GEOD-45194 | biostudies-arrayexpress
Project description:The adaptor protein MERIT40 is a core subunit of deubiquitinating (DUB) complexes that specifically cleave Lysine63-polyubiquitin chains. We found that MERIT40 is an important negative regulator of hematopoietic stem cell (HSC) homeostasis, quiescence and self-renewal. This study aims to investigate the molecular mechanism by which MERIT40 regulates HSC expansion and cell cycle. We performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from WT and Merit40-/- mice. Results identify select MERIT40-mediated pathways with potential involvement in HSC cell cycle regulation. CD150+CD48-LSK HSCs were double sorted from WT and Merit40-/- mice at young age. RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the PENN Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 2.0ST array (Affymetrix).
2015-04-01 | E-GEOD-65245 | biostudies-arrayexpress
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
Project description:Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others.
2014-03-14 | GSE45194 | GEO
Project description:The adaptor protein MERIT40 is a core subunit of deubiquitinating (DUB) complexes that specifically cleave Lysine63-polyubiquitin chains. We found that MERIT40 is an important negative regulator of hematopoietic stem cell (HSC) homeostasis, quiescence and self-renewal. This study aims to investigate the molecular mechanism by which MERIT40 regulates HSC expansion and cell cycle. We performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from WT and Merit40-/- mice. Results identify select MERIT40-mediated pathways with potential involvement in HSC cell cycle regulation.
2015-04-01 | GSE65245 | GEO
Project description:The transcription factor SOX17 is expressed by fetal, but not adult hematoipoietic stem cells (HSCs), and is required for the maintenance of fetal and neonatal, but not adult, HSCs. In the current study we show that ectopic expression of Sox17 in adult HSCs and transiently reconstituting multipotent progenitors was sufficient to confer increased self-renewal potential and the expression of fetal HSC genes including fetal HSC surface markers. To assess the mechanisms by which ectopic Sox17 expression in adult hematopoietic progenitors increased self-renewal potential and conferred fetal HSC properties, we compared the gene expression profiles of E16.5 fetal liver HSCs, young adult bone marrow HSCs, young adult bone marrow CD48+LSK cells, and Sox17-expressing CD48+LSK cells isolated from mice that had been transplanted with MSCV-Sox17-infected bone marrow cells 12 weeks earlier. Total RNA (~5ng) was isolated from 3 independent, freshly isolated aliquots of 10,000 E16.5 fetal liver HSCs, 10,000 fetal liver CD48+LSK cells, 10,000 adult bone marrow HSCs, 10,000 adult bone marrow CD48+LSK cells, 10,000 Sox17-expressing CD48+LSK cells isolated from primary recipients 12 weeks after transplantation of MSCV-Sox17-infected bone marrow cells. Purified RNA was reverse transcribed and amplified using the WT-Ovation™ Pico RNA Amplification system (NuGEN Technologies) following the manufacturer’s instructions. Sense strand cDNA was generated using WT-Ovation™ Exon Module (NuGEN), then fragmented and labeled using the FL-Ovation™ cDNA Biotin Module V2 (NuGEN). 2.5µg of labeled cDNA were hybridized to Affymetrix Mouse Gene ST 1.0 microarrays.
2011-07-14 | E-GEOD-30444 | biostudies-arrayexpress
Project description:The adaptor protein Lnk is an important negative regulator of HSC homeostasis and self-renewal. This study aims to investigate the role of Lnk in HSC aging. Here we performed expression profiling of bone marrow CD150+CD48-LSK LT-HSCs from young and old WT and Lnk-/- mice. Results identify select Lnk-mediated pathways with potential involvement in HSC self-renewal and aging. CD150+CD48-LSK HSCs were double sorted from WT and Lnk-/- mice at both young and old ages (2 months and 20 months, respectively). RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the Penn Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 1.0ST array (Affymetrix).
2012-10-03 | E-GEOD-39553 | biostudies-arrayexpress