Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Haemopedia: An Expression Atlas of Murine Haematopoietic Cells

ABSTRACT: Haematopoiesis is a multi-stage process that involves the differentiation of multipotent stem cells and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, a comprehensive atlas of murine gene expression data that covers all the mature lineages in haematopoiesis, including rare cell populations such as eosinophils, mast cells, basophils and megakaryocytes and a large collection of progenitor and stem cells. We have used this dataset to identify gene sets with specifically enriched expression in each of the mature blood cell lineages. Many of the genes in these sets show conserved lineage-enriched expression patterns in human haematopoiesis. We also identify some genes with divergent expression patterns between mouse and human, highlighting species specific differences in blood cell production. To make analyses of Haemopedia and other blood cell transcriptional datasets easier, we have created an online web portal, Haemosphere, which provides simple tools to interrogate gene expression-based relationships between haematopoietic cell types and genes of interest. Total RNA was obtained from 54 haematopoetic cells types and 8 non-haematopoietic out groups.

ORGANISM(S): Mus musculus

SUBMITTER: Carolyn de Graaf

PROVIDER: E-GEOD-77098 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Stem cell differentiation and lineage specification depend on coordinated programs of gene expression, but our knowledge of the chromatin modifying factors regulating these events remains incomplete. Ubiquitination of histone H2A (H2A-K119u) is a common chromatin modification associated with gene silencing, and controlled by the ubiquitin-ligase polycomb repressor complex 1 (PRC1) and H2A-deubiquitinating enzymes (H2A-DUBs). The roles of H2A-DUBs in mammalian development, stem cells, and haematopoiesis have not been addressed. Here we characterized an H2A-DUB targeted mouse line Mysm1-tm1a/tm1a and demonstrated defects in bone marrow haematopoiesis, resulting in lymphopenia, anemia, and thrombocytosis. Development of lymphocytes was impaired from the earliest stages of their differentiation; and there was also a depletion of erythroid cells and a defect in erythroid progenitor function. These phenotypes were due to a cell-intrinsic requirement for Mysm1 in the bone marrow. Importantly, Mysm1-tm1a/tm1a haematopoietic stem cells were functionally impaired, and this was associated with elevated levels of reactive oxygen species, γH2AX DNA damage marker, and p53 protein in the haematopoietic progenitors. Overall these data establish a role for Mysm1 in the maintenance of bone marrow stem cell function, in the control of oxidative stress and genetic stability in haematopoietic progenitors, and in the development of lymphoid and erythroid lineages. Total RNA from different mouse tissues (liver, bone marrow, brain) and cell types (embryonic fibroblasts - MEFs, and embryonic stem cells - ESCs) from wild type, Mysm1+/tm1a (heterozygous), and Mysm1tma1/tm1a (homozygous) mice was analyzed. Tissue and MEFs comparisons are between 3-4 animals per group; ESC comparisons are between three independently passaged samples of wild type, Mysm1+/tm1a, and Mysm1tma1/tm1aES-cells, all on C57BL/6 background. Full allele name: Mysm1tm1a(KOMP)WTSI . This Series includes the data from the tissues.

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Haemopedia: An Expression Atlas of Murine Haematopoietic Cells

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