Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression analysis of adult and fetal T-cell progenitors

ABSTRACT: Development of T-cells provides a unique opportunity to study cell-fate determination due to the accessability and the well defined stages of developmental stages. In order to understand the genetic programs underlying fetal and adult T‑cell fate specification we subjected highly purified fetal and adult T-cell progenitor populations to a genome‑wide transcriptional analysis. The aim was to identify molecular elements that govern T-cell fate specification as a whole but ultimately to isolate elements that were specific for a given population in a specific developmental window. FACS purified ETP, DN2 and DN3 progenitor thymocytes from C57BL/6 adult mice and E14.5 embryos were hybridised to Affymetrix Mouse Genome 430A_2.0 GeneChip Arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Nikolai Belyaev

PROVIDER: E-GEOD-24142 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages.

Belyaev Nikolai N NN Biró Judit J Athanasakis Dimitrios D Fernandez-Reyes Delmiro D Potocnik Alexandre J AJ

Immunogenetics 20120513 8

T cell development constitutes a multistage process allowing the dissection of events resulting in cellular commitment and functional specification in a specialized microenvironment. This process is guided by the appropriate expression of regulatory genetic factors like transcriptional activators or repressors which are, in part, dependent on instructive signals of the microenvironment. To date, it remains unclear whether exactly the same genetic mechanism acts in adult compared to fetal T cell ...[more]

PMID: 22581009

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Project description:Epigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45α, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions. mRNA expression of 8 hematopoietic progenitor populations [MPPFL-(5), MPPFL+(3), CMP(3), GMP(3), CLP(3), DN1(3), DN2(3), DN3(3)] were compared

Dataset Information

Gene expression analysis of adult and fetal T-cell progenitors

Publications

Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages.

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