title: A critical role for TCF-1 in T-lineage specification and differentiation.
abstract: The vertebrate thymus provides an inductive environment for T-cell development. Within the mouse thymus, Notch signals are indispensable for imposing the T-cell fate on multipotential haematopoietic progenitors, but the downstream effectors that impart T-lineage specification and commitment are not well understood. Here we show that a transcription factor, T-cell factor 1 (TCF-1; also known as transcription factor 7, T-cell specific, TCF7), is a critical regulator in T-cell specification. TCF-1 is highly expressed in the earliest thymic progenitors, and its expression is upregulated by Notch signals. Most importantly, when TCF-1 is forcibly expressed in bone marrow (BM) progenitors, it drives the development of T-lineage cells in the absence of T-inductive Notch1 signals. Further characterization of these TCF-1-induced cells revealed expression of many T-lineage genes, including T-cell-specific transcription factors Gata3 and Bcl11b, and components of the T-cell receptor. Our data suggest a model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upregulating expression of T-cell essential genes.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brittany Nicole
authors.initials: BN
authors.lastname: Weber
authors.forename: Anthony Wei-Shine
authors.initials: AW
authors.lastname: Chi
authors.forename: Alejandro
authors.initials: A
authors.lastname: Chavez
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yashiro-Ohtani
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Olga
authors.initials: O
authors.lastname: Shestova
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D020043:Genes, Essential; D057809:HEK293 Cells; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D051822:T Cell Transcription Factor 1