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Gene expression signatures of Meis1 conditional knockout hematopoietic stem cells

ABSTRACT: Meis1 encodes a TALE family homeodomain protein that was first identified as a common retroviral integration site in mouse BHX2 myeloid leukemia. It functions as a DNA binding co-factor of Hox proteins through interacting with Pbx, a member of another TALE family protein. Moreover, Meis1 homozygous knockout mice are embryonic lethal, showing significant defects in vasculogenesis, eye development and hematopoiesis. Severe defects were also observed in adult hematopoiesis by conditional inactivation of Meis1 in vivo. Meis1 is critical to maintain the balance between enter and exit from cell cycles of hematopoietic stem cells (HSCs), indicating that Meis1 regulates self-renewal and quiescence of HSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE38336 | GEO | 2013/12/01

SECONDARY ACCESSION(S): PRJNA167683

REPOSITORIES: GEO

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Gene expression signatures of Meis1 conditional knockout hematopoietic stem cells

Project description:Meis1 encodes a TALE family homeodomain protein that was first identified as a common retroviral integration site in mouse BHX2 myeloid leukemia. It functions as a DNA binding co-factor of Hox proteins through interacting with Pbx, a member of another TALE family protein. Moreover, Meis1 homozygous knockout mice are embryonic lethal, showing significant defects in vasculogenesis, eye development and hematopoiesis. Severe defects were also observed in adult hematopoiesis by conditional inactivation of Meis1 in vivo. Meis1 is critical to maintain the balance between enter and exit from cell cycles of hematopoietic stem cells (HSCs), indicating that Meis1 regulates self-renewal and quiescence of HSCs. Total RNA was isolated from KSL cells obtained from poly(I:C)-treated Mx1-Cre Meis1fl/fl and sham-treated Meis1fl/fl mice.

2013-12-01 | E-GEOD-38336 | biostudies-arrayexpress

Meis1 deficiency effect on thymic epithelial cells

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Meis1 deficiency effect on thymic epithelial cells

Project description:Analysis of thymic epithelial cells lacking Meis1 gene using K14-CreERT2 Meis1fl/fl mice. Meis1 is a TALE class homeodomain transcription factor that critically regulates numerous embryonic developmental processes. Results provide insight into the role of Meis1 in the maintenance of postnatal thymic epithelial cells. Meis1-regulated gene expression in CD45- EpCAM+ mouse thymic epithelial cells was measured at 4 days after the induction of Meis1 deletion. Two independent experiments (pools of 6 mice; 2 pools per genotype) were performed.

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Genome-wide maps of Meis1, Hoxa9 and Pbx binding sites in murine myeloid leukemia cells

Project description:We have searched genome-wide binding sites of homeodomain proteins important for leukemogenesis in Hoxa9- and Meis1- induced myeloid leukemia cells. Thousands of binding sites of these three family proteins have been identified and many of them are co-localized with those of each others. Hoxa9 and Pbx binding sites were compared between the presence and absence of Meis1 by its knockout in the same cells. In combination of the results with gene expression profiles of the same cells, important downstream target genes of Meis1 in leukemogenesis have been identified.

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Transcriptional signatures of thymic epithelial cells with distinct Meis1 expression levels

Project description:Analysis of thymic epithelial cells with distinct Meis1 gene expression levels using Meis1-EGFP reporter mice. Meis1 is a TALE class homeodomain transcription factor that critically regulates numerous embryonic developmental processes. Results provide insight into the role of Meis1 in the maintenance of postnatal thymic epithelial cells. Gene expression in CD45- EpCAM+ thymic epithelial cells with distinct Meis1 expression levels (Meis1high, Meis1low and Meis1-) was measured by using Meis1-EGFP BAC-transgenic reporter mice. Two independent experiments (pools of 6 mice; 2 pools per genotype) were performed.

2012-11-30 | E-GEOD-30825 | biostudies-arrayexpress

Gene expression profiling of control and Meis1 deleted bone marrow

Project description:The transcription factor Meis1 is preferentially expressed in hematopoietic stem cells (HSCs) and over-expressed in certain leukemias. However, the functions of Meis1 in hematopoiesis remain largely unknown. Using inducible knock-out mice, we found that Meis1 is required for the maintenance of hematopoiesis under stress and over long term while steady-state hematopoiesis was sustained in the absence of Meis1. Bone marrow cells of Meis1 deficient mice showed reduced colony formation, contained significantly fewer numbers of long- term HSCs and these Meis1-deficient HSCs exhibited loss of quiescence. Further, we found that Meis1 deletion led to the accumulation of reactive oxygen species (ROS) in HSCs and decreased expression of genes implicated in hypoxia response. Finally, ROS scavenging by N-acetyl cysteine or stabilization of hypoxia-signaling by knockdown of the VHL protein led to reversal of the effects of Meis1-deletion. Taken together, these results demonstrate that Meis1 protects and preserves HSCs by restricting oxidative metabolism. Lineage negative cells were harvested from Meis1-flox/CreER or control mice and incubated with 4-OHT for 48 hours. Total RNA was extracted and used for the profiling experiment.

2012-09-26 | E-GEOD-41133 | biostudies-arrayexpress

Gene expression profiling of control and Meis1 deleted bone marrow

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Identification of gene targets of Meis1

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Identification of gene targets of Meis1

Project description:The homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo. Our present study suggested it exerts two distinguishable effects in differentiating ES cells. First, it increases the numbers of hematopoietic progenitors and extends their persistence in culture. Second, Meis1 skews hematopoietic differentiation by suppressing erythroid while enhancing megakaryocytic progenitor differentiation. To identify the underlying transcriptional bases of these actions, we carried out microarray analysis to compare the various populations of cells developing in ES differentiation cultures in the presence and absence of Meis1 induction. ES cells with dox-inducible Meis1 (A2lox.Meis1) were differentiated as embryoid bodies (EBs) for 6 days before plating on OP9-GFP cell monolayers and cytokines, and treated with (+) or without (-) doxycycline (dox). Cells were purified by cell sorting on day 7 or 8 into various populations based on levels of CD41 expression: GFP-CD41-, GFP-CD41+ (day 7) and GFP-CD41-,GFP-CD41int, and GFP-CD41hi (day 8). Gene expression of these purified populations was determined by microarray analysis.

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