Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Musashi 2 is a regulator of the hematopoietic stem cell compartment identified by a retroviral insertion screen and knockout mice

ABSTRACT: We have used a retroviral integration screen to search for novel genes that regulate hematopoietic stem cell (HSC) function. One of the genes that conferred HSC dominance when overexpressed due to an adjacent retroviral insertion was Musashi 2 (Msi2), an RNA binding protein that can act as a translational inhibitor. A gene trap mouse model that inactivates the gene shows that Msi2 is more highly expressed in long term (LT) and short term (ST) HSCs as well as in lymphoid myeloid primed progenitors (LMPPs), but much less in intermediate progenitors and mature cells. Mice lacking Msi2 are fully viable up to more than a year but exhibit severe defects in primitive precursors, most significantly a reduction in the number of ST-HSCs and LMPPs and a decrease of leukocyte numbers, effects that are exacerbated with age. Cell cycle and gene expression analyses suggest that the main hematopoietic defect in Msi2 defective mice consists in a decreased proliferation capacity of ST-HSCs and LMPPs. In addition, HSCs lacking Msi2 are severely impaired in competitive repopulation experiments, being overgrown by wild type cells even when mutant cells were provided in excess. Our data indicate that Msi2 maintains the stem cell compartment mainly by regulating the proliferation of primitive progenitors downstream of LT-HSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE29432 | GEO | 2011/05/21

SECONDARY ACCESSION(S): PRJNA141505

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Musashi 2 is a regulator of the hematopoietic stem cell compartment identified by a retroviral insertion screen and knockout mice

Project description:We have used a retroviral integration screen to search for novel genes that regulate hematopoietic stem cell (HSC) function. One of the genes that conferred HSC dominance when overexpressed due to an adjacent retroviral insertion was Musashi 2 (Msi2), an RNA binding protein that can act as a translational inhibitor. A gene trap mouse model that inactivates the gene shows that Msi2 is more highly expressed in long term (LT) and short term (ST) HSCs as well as in lymphoid myeloid primed progenitors (LMPPs), but much less in intermediate progenitors and mature cells. Mice lacking Msi2 are fully viable up to more than a year but exhibit severe defects in primitive precursors, most significantly a reduction in the number of ST-HSCs and LMPPs and a decrease of leukocyte numbers, effects that are exacerbated with age. Cell cycle and gene expression analyses suggest that the main hematopoietic defect in Msi2 defective mice consists in a decreased proliferation capacity of ST-HSCs and LMPPs. In addition, HSCs lacking Msi2 are severely impaired in competitive repopulation experiments, being overgrown by wild type cells even when mutant cells were provided in excess. Our data indicate that Msi2 maintains the stem cell compartment mainly by regulating the proliferation of primitive progenitors downstream of LT-HSCs. RNA from 2 different cell populations (LSK cells and KIT+ cells) were analyzed for both wildtype and Msi2-/- null samples. Two technical replicates were analyzed for the KIT+ samples and three technical replicates were analyzed for the LSK samples.

2011-05-21 | E-GEOD-29432 | biostudies-arrayexpress

Gene expression profiling of LT-HSCs and ST-HSCs conditionally expressing MLL-ENL

Project description:We have developed a new conditional transgenic mouse showing that MLL-ENL, at an endogenous-like expression level, induces leukemic transformation selectively in LT-HSCs. To investigate the molecular mechanism of leukemic transformation in LT-HSCs conditionally expressing MLL-ENL, we preliminarily performed comprehensive gene expression profiling of CreER-transduced LT-HSCs and ST-HSCs using cDNA microarray analysis. For initial screening of candidate genes invloved in the leukemic transformation, total RNA was extracted from colony-forming cells derived from LT-HSCs and ST-HSCs transduced with CreER or mock. Four samples were analyzed, and CreER-transduced LT/ST-HSC-derived cells were compared with mock-transduced LT/ST-HSC-derived cells, while CreER/mock-transduced LT-HSC-derived cells were compared with CreER/mock-transduced ST-HSC-derived cells.

2013-07-17 | E-GEOD-48539 | biostudies-arrayexpress

LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells

Project description:Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) of Ltbr-deficient and -proficient LT/ST-HSCs isolated from chimeric mice. Methods: Transcriptomic profiles of Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice 6 weeks after reconstitution were assessed in triplicate by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: We mapped about 60 million sequence reads per sample to the mouse genome (GRCm38 - mm10) and identified expressed transcripts in Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice. RNA-seq. data confirmed stable expression of known housekeeping genes. Differentially expressed genes between the Ltbr-/- and Ly5.1 LT/ST-HSCs were identified with a fold change ≥1.5 and FDR p-value <0.05. Conclusions: Our study represents the first detailed transcriptome analysis of Ltbr-deficient and -proficient LT/ST-HSCs, with biologic replicates, generated by RNA-seq. technology. Our results show that Ltbr signaling regulates HSC proliferation and differentiation. Evaluation of mRNA content in Ltbr-/- LT/ST-HSCs revealed that Ltbr-deficiency enhances HSC proliferation, differentiation, cell cycle and reduces the activity of canonical NFkB signaling.

2020-10-23 | GSE141206 | GEO

Transcriptomic analysis of the early effects of sex steroid ablation on BM LT-HSCs 2 days post surgery.

Project description:Analysis of gene-expression alterations in primitive LT-HSCs as early as 2 days post sex steroid ablation. This study aimed to determine potential intrinsic changes occuring in the LT-HSC population associated with sex steroid ablation (SSA) at a timepoint that preceeded the earliest reported functional hematopoietic enhancements occuring at day 7 post SSA. These results are vital in providing insight into the role of LT-HSCs in initiating SSA-mediated immune regeneration. Total RNA obtained from BM-sorted LT-HSC 2 days after sex steroid ablation compared to sham sex steroid ablation controls.

2015-03-01 | E-GEOD-64841 | biostudies-arrayexpress

HyperTRIBE uncovers MSI2 increased RNA binding activity and differential regulation in leukemic stem cells [LSK cells]

Project description:Understanding RBPs’ molecular functions as well as their cell-type specific activity requires identification of RBPs’ direct mRNA targets. However, efforts to identify RNA targets of RNA binding proteins in stem cells have been hindered by limited cell numbers. Here we adapted the HyperTRIBE method using an RBP fused to a Drosophila RNA editing enzyme (ADAR) to allow for global mapping of mRNA targets of the RBP MSI2 in rare mammalian adult stem cells. We applied this method to identify MSI2 RNA binding targets in subcompartments of mouse HSPCs including long-term HSCs (LT-HSCs), short-term HSCs (ST-HSCs), multipotent progenitors MPP2 and MPP4. MSI2 fusion with the catalytic domain of the Hyperactive ADAR mutant (MSI2-ADA) or with the dead catalytic mutant (MSI2-DCD) were overexpressed in sorted LSK cells, which were transplanted into mice. After 7 weeks, mouse HSPCs were sorted into 4 populations for RNA-seq. As ADAR converts A to I (G), the fusion leaves a "finger-print" where MSI2 binds. MSI2-DCD and empty vector controls were used to normalize the background editing. We were able to identify MSI2 RNA binding targets in hematopoietic stem and progenitor cells for the first time. Furthermore, we show differential RNA binding activity (by target transcripts and editing frequency) of MSI2 in different subcompartments of HSPCs.

2020-03-11 | GSE132947 | GEO

Chromatin remodeling and dynamics of hematopoietic stem cells and progenitors

Project description:Hematopoietic stem cells (HSCs) have the capability to self-renew and differentiate into all blood cell lineages. How chromatin state regulates self-renewal and differentiation of HSC is not fully understood. Here, we provided the first global landscape of chromatin state in long term (LT)-HSCs, short term (ST)-HSCs and multipotent progenitor (MPP) by ATAC-seq analysis. We discovered that the promoter regions of genes that control cell cycle, and several important miRNAs were maintained as open chromatin state in HSCs. In addition, we found that promoter-TSS regions of many genes were occupied by nucleosomes in LT/ST-HSC and they become open chromatin regions in MPP. Furthermore, we uncovered 166 known transcription factors (TFs) including C/EBPs, GABPA, and FLI1can access to the promoter open chromatin in HSCs, and quarter of them displayed cell type-specific manner. Among them, we identified DNA cis-element of Krüppel-like factor family (KLF9, KLF10 and KLF14) were specifically enriched in LT-HSC. Meanwhile, we found that 8299 enhancers are established concomitantly with the formation of open chromatin sites, and they can be accessed by 153 TFs including GABPA, CTCF and RNUX1/RUNX2. Near hundred TF-binding motif are enriched in both promoter and enhancers, indicating they may direct the interaction between promoters and enhancers. Finally, we found 21.7% poised enhancers were preset in LT/ST-HSCs, and became active enhancers in MPP. Together, our finding provides new insightinto how chromatin state and transcriptionalregulatory networkare remodeledin promoter and enhancer regions during the differentiation of LT/ST-HSC to MPP.

2017-06-05 | GSE84959 | GEO

Transcription profiling of mouse normal LT-HSC vs ST-HSC

Project description:Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. Experiment Overall Design: LT-HSC (Lin-cKit+Sca1+CD34-CD135-) and ST-HSC (Lin-cKit+Sca1+CD34+CD135-) cells were prospectively sorted from the BM of MxCre-.Pbx1f/f control mice harvested 4 weeks after the last injection of poly(I:C).

2008-06-20 | E-GEOD-9189 | biostudies-arrayexpress

Time-course analysis of transcriptomes of human long-term (LT) and short-term (ST) hematopoietic stem cells (HSC) after xenotransplantation

Project description:Here we tracked transcriptional changes in LT, ST-HSC and MLP after transplantation into immunocompromised mice. We show that LT- and ST-HSC activate similar pathways upon transplantation but they modulate distinct sets of genes. Total RNA was obtained from flow-sorted populations of human LT-, ST-HSC and MLP isolated from cord blood or immunocompromised mice transplanted with human at hematopoeitic progenitors at different time points after transplantation.

2015-02-20 | E-GEOD-58299 | biostudies-arrayexpress

Expression data of freshly isolated and sorted HSC populations from murine fetal liver or adult bone marrow [array]

Project description:We isolated murine fetal liver and murine adult bone marrow and FACS sorted LT-HSCs, ST-HSCs and MPPs. We used global expression analysis by microarray to compare regulated genesets in different HSC populations in fetal and adult.

2023-04-30 | GSE173158 | GEO

RNA-sequencing analysis of murine Hematopoietic Stem Cells treated with Nicotinamide Riboside

Project description:LT-HSC and ST-HSCs were FACS sorted (>10^4cells per sample), cultured for two days in presence or absence of 1 mM NR and total RNA extracted

2019-01-17 | GSE125211 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data