Open AccessNOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development
Author(s) -
Jie Li,
Gordon Jack,
Edward L. Y. Chen,
Shiyun Xiao,
Luying Wu,
Juan Carlos ZúñigaPflücker,
Nancy R. Manley
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.178988
Subject(s) - biology , notch signaling pathway , progenitor cell , progenitor , microbiology and biotechnology , signal transduction , cellular differentiation , lineage (genetic) , stem cell , immunology , genetics , gene
The cortical and medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage commitment, T cell positive selection and the establishment of self-tolerance, but the mechanisms controlling their fetal specification and differentiation are poorly understood. Here, we show that Notch signaling is required to specify and expand the mTEC lineage. Notch1 is expressed by and active in TEC progenitors. Deletion of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mTEC specification and progenitor expansion. Conversely, forced Notch signaling in all TEC resulted in widespread expression of mTEC progenitor markers and profound defects in TEC differentiation. In addition, lineage-tracing analysis indicated that all mTECs have a history of receiving a Notch signal, consistent with Notch signaling occurring in mTEC progenitors. These data provide strong evidence for a requirement for Notch signaling in specification of the mTEC lineage.