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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse long or short term hematopoietic stem cells and the proto-oncogene Pbx1 (GEO Super Series)

ABSTRACT: This SuperSeries is composed of the following subset Series:; GSE9188: Differentially regulated genes in LT-HSC from control or Pbx1-null mice; GSE9189: Differentially regulated genes in normal LT-HSC vs ST-HSC Experiment Overall Design: Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Francesca Ficara

PROVIDER: E-GEOD-9198 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence.

Ficara Francesca F Murphy Mark J MJ Lin Min M Cleary Michael L ML

Cell stem cell 20080501 5

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. Transcriptio ...[more]

PMID: 18462698

Similar Datasets

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

Transcription profiling of mouse long term HSC from control or Pbx1-null mice

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. A significant proportion of Pbx1-dependent genes are associated with the Tgf-b pathway, which serves a major role in maintaining HSC quiescence. Pbx1-deficient LT-HSCs are unable to up-regulate the cyclin dependent kinase inhibitor p57 in response to Tgf-b, providing a mechanism through which Pbx1 maintenance of stem cell self-renewal is achieved. Experiment Overall Design: Highly efficient Pbx1 deletion was induced with poly(I:C) in 3 young MxCre+.Pbx1f/f mutant or 2 MxCre-.Pbx1f/f control mice. LT-HSC (Lin-cKit+Sca1+CD34-CD135-) cells were prospectively sorted from bone marrow of individual mice harvested 4 weeks after the last injection of poly(I:C).

2008-06-20 | E-GEOD-9188 | biostudies-arrayexpress

RNA Seq of control and Cyp26b1 knockout mouse longterm hematopoietic stem cells

Project description:The transcriptome of Ctrl and Cyp26b1KO longterm hematopoietic stem cells (LT-HSC) was assessed by RNAseq.

2021-11-02 | E-MTAB-9745 | biostudies-arrayexpress

RNA Seq of 7-month old control and Cyp26b1KO LT-HSCs

Project description:The transcriptome of Ctrl and Cyp26b1KO longterm hematopoietic stem cells (LT-HSC) of 7-month old mice was assessed by RNAseq.

2021-11-02 | E-MTAB-10659 | biostudies-arrayexpress

Differentially regulated genes in control and c-myc N-myc deficient LT-HSCs

Project description:Analysis of HSCs from control and c-myc N-myc deficient long-term hematopoietic stem cells. HSCs lacking both c-myc and N-myc display increased apoptosis rates. Data provide insight into the molecular changes occuring upon complete loss of Myc activity, clarifying the resulting apoptotic mechanism and the role of Myc family proteins in HSCs. LT-HSC (Lin-Sca1+CD150+CD48-) cells were sorted from the BM of MxCre c-myc flox2 N-myc flox2 (experimental) and c-myc flox2 N-myc flox2 (control) mice 3 days after the last pI-pC injection. Each condition was analysed in triplicates, with each replicate consisting of a pool of 3 dKO mice or 2 control mice.

2009-02-20 | E-GEOD-12467 | biostudies-arrayexpress

Expression data for conditional Dnmt1knockout hematopoietic stem and progenitor cells

Project description:DNA methylation is essential for mammalian development and plays crucial roles in a variety of biological processes. The DNA methyltransferase Dnmt1 serves to maintain parental cell methylation patterns on daughter DNA strands in mitotic cells, however, the precise role of Dnmt1 in regulation of quiescent adult stem cells is not known. To examine the role of Dnmt1 in adult hematopoietic stem cells (HSCs), we conditionally disrupted Dnmt1 in the hematopoietic system. We used microarrays to profile the global gene expression program in hematopoietic stem and progenitor cells following deletion of Dnmt1. Dnmt1 was conditionally deleted in the hematopoietic system by injections of poly(I)poly(C) to induce Cre expression from the Mx-Cre transgene. Control mice were also injected with poly(I)poly(C) but do not carry the Mx-Cre transgene. Four days after completion of poly(I)poly(C) injections, bone marrow was harvested from the mice, antibody-mediated magnetic bead selection was used to remove cells expressing mature lineage markers, and the resulting lineage-depleted cells were stained with fluorochrome-conjugated antibodies against the surface receptors c-Kit, Sca-1 and CD34. Populations of LT-HSCs, MPPs and myeloid progenitors were FACS sorted, RNA was extracted and amplified from these sorted populations and hybridized to Affymetrix microarrays to compare changes in gene expression induced by conditional knockout of Dnmt1 compared to control in each of the three cell populations. There are 2 biological replicates for the LT-HSCs and MPPs and 3 biological replicates for the myeloid progenitors.

2010-03-03 | E-GEOD-15840 | biostudies-arrayexpress

Expression data from control and LRF (leukemia/lymphoma related factor)-deficient mouse LT-HSCs

Project description:LRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis. We performed gene expression microarray analysis of FACS-sorted LT-HSCs (LSK IL7Ra-Flt3-CD150+CD48-) to assess the effect of Lrf loss on the LT-HSC transcriptome. Zbtb7a Flox/+ Mx1-Cre+ mice were used as a control to normalize the potential effects of Cre recombinase. LT-HSCs were FACS-sorted from three Lrf knockout (Zbtb7a Flox/Flox Mx1-Cre+) and two control (Zbtb7a Flox/+ Mx1-Cre+) mice, nine days after the first pIpC injection.

2012-10-26 | E-GEOD-41839 | biostudies-arrayexpress

The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [Low-C]

Project description:Life-long blood production requires long-term hematopoietic stem cells (LT-HSC) - marked by stemness states involving quiescence and self-renewal - to transition into activated short-term HSC (ST-HSC) with reduced stemness. As few transcriptional changes underlie this transition, we used single-cell and bulk ATAC-seq on human HSC and stem/progenitor subsets (HSPC) to uncover chromatin accessibility signatures, one including LT-HSC (LT/HSPC signature) and another excluding LT-HSC (Act/HSPC signature). These signatures inversely correlated during early hematopoietic commitment and differentiation. The Act/HSPC signature contains CTCF binding sites mediating 351 chromatin interactions, engaged in ST-HSC but not LT-HSC, enclosing multiple stemness pathway genes active in LT-HSC and repressed in ST-HSC. CTCF silencing derepressed stemness genes, restraining quiescent LT-HSC from transitioning to activated ST-HSC. Hence, 3D chromatin interactions centrally mediated by CTCF, endow a gatekeeper function that governs the earliest fate transitions HSC make by coordinating disparate stemness pathways linked to quiescence and self-renewal.

2020-11-23 | GSE159287 | GEO

Transcription profiling of mouse AIN-centered DCN of delayed-type eyeblink conditioned mice (GEO Super Series)

Project description:This SuperSeries comprises the following subset Series:; GSE3651: The AIN-centered DCN of delayed-type eyeblink conditioned mice: 3-d paired training and sham negative control groups; GSE3652: The AIN-centered DCN of delayed-type eyeblink conditioned mice: 7-d paired and 7-d unpaired training groups; Anterior interpositus nucleus (AIN) is a proposed site of memory formation of eyeblink conditioning. A large part of the underlying molecular events, however, remains unknown. To elucidate molecular mechanisms, we examined transcriptional changes in the AIN of mice trained with delayed-type eyeblink conditioning; The data are not directly comparable between GSE3651 and GSE3652, given the different experimental time periods and amounts of cRNA used for hybridizations. Experiment Overall Design: Refer to individual Series

2008-06-12 | E-GEOD-3713 | 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

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