In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 31 ( 2020-07-31)
Abstract:
T cell factor 1 (Tcf1) is the first T cell–specific protein induced by Notch signaling in the thymus, leading to the activation of two major target genes, Gata3 and Bcl11b . Tcf1 deficiency results in partial arrests in T cell development, high apoptosis, and increased development of B and myeloid cells. Phenotypically, seemingly fully T cell–committed thymocytes with Tcf1 deficiency have promiscuous gene expression and an altered epigenetic profile and can dedifferentiate into more immature thymocytes and non-T cells. Restoring Bcl11b expression in Tcf1-deficient cells rescues T cell development but does not strongly suppress the development of non-T cells; in contrast, expressing Gata3 suppresses their development but does not rescue T cell development. Thus, T cell development is controlled by a minimal transcription factor network involving Notch signaling, Tcf1, and the subsequent division of labor between Bcl11b and Gata3, thereby ensuring a properly regulated T cell gene expression program.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aaw7313
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
detail.hit.zdb_id:
2810933-8
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