An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants.

Cellular differentiation of the T-cell branch of the immune system begins with the hematopoietic stem cell, which undergoes a series of stages characterized by progressive restriction in multipotency and acquisition of specific lineage identity At the molecular level, the restriction of cell potential, commitment and differentiation to a specific lineage is achieved through the coordinated control of gene expression and epigenetic mechanisms. Here we analyzed and compared the gene expression profiles and the genome-wide histone modification marks H3K4me3 and H3K27me3 in i) in vitro propagated hematopoietic stem cells, ii) in vitro generated and propagated pro T dells derived from these stem cells and iii) Double positive thymocytes derived from these pro T cells after injection into Rag deficient mice. The combined analyses of the different datasets in this unique experimental system, highlighted the importance of both transcriptional and epigenetic repression in shaping the early phases of T-cell development. This article is protected by copyright. All rights reserved.