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

• Main Authors: Vigano, Maria Alessandra, Ivanek, Robert, Balwierz, Piotr, Berninger, Philipp, van Nimwegen, Erik, Karjalainen, Klaus, Rolink, Antonius
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Medicine
• Online Access: https://hdl.handle.net/10356/101205; http://hdl.handle.net/10220/19707
• Institution: Nanyang Technological University

Cellular differentiation of the T-cell branch of the immune system begins with the HSC, 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 (H3 lysine 4 trimethylation) and H3K27me3 (H3 lysine 27 trimethylation) in (i) in vitro propagated HSCs, (ii) in vitro generated and propagated pro-T cells 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.