title: An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants.
abstract: 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.
authors.affiliation: Developmental and Molecular Immunology Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Vigano
authors.forename: Robert
authors.initials: R
authors.lastname: Ivanek
authors.forename: Piotr
authors.initials: P
authors.lastname: Balwierz
authors.forename: Philipp
authors.initials: P
authors.lastname: Berninger
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.forename: Klaus
authors.initials: K
authors.lastname: Karjalainen
authors.forename: Antonius
authors.initials: A
authors.lastname: Rolink
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D006657:Histones; D008239:Lysine
keywords: Development; Epigenetics; Genome-wide; T cells