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RORa expression is a critical checkpoint for the bifurcation of the T cell and ILC2 lineages in the embryonic thymus

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE146745 | GEO | 2020/11/03

REPOSITORIES: GEO

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RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus.

Project description:Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4+CD8+ (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORα repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORα overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORα expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.

| S-EPMC7116838 | biostudies-literature

RORa expression is a critical checkpoint for the bifurcation of the T cell and ILC2 lineages in the embryonic thymus

Project description:RORa expression is a critical checkpoint for the bifurcation of the T cell and ILC2 lineages in the embryonic thymus

| PRJNA611788 | ENA

Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus.

Project description:Innate lymphoid cells (ILCs) are important regulators in various immune responses. The current paradigm states that all newly made ILCs originate from common lymphoid progenitors in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Unexpectedly, we found that ectopically expressing Id1 or deleting two E protein genes in the thymus drastically increased ILC2 counts in the thymus and other organs where ILC2 normally reside. Further evidence suggests a thymic origin of these mutant ILC2s. The mutant mice exhibit augmented spontaneous infiltration of eosinophils and heightened responses to papain in the lung and increased ability to expulse the helminth parasite, Nippostrongylus brasiliensis These results prompt the questions of whether the thymus naturally has the capacity to produce ILC2s and whether E proteins restrain such a potential. The abundance of ILC2s in Id1 transgenic mice also offers a unique opportunity for testing the biological functions of ILC2s.

| S-EPMC5404348 | biostudies-literature

Epigenetic restriction of embryonic and extraembryonic lineages mirrors the somatic transition to cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-09-18 | GSE84236 | GEO

Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-10-30 | GSE131368 | GEO

Cell competition is a tumor suppressor mechanism in the thymus.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-16 | E-GEOD-56419 | biostudies-arrayexpress

REGION-SPECIFIC NEURAL STEM CELL LINEAGES REVEALED BY SINGLE-CELL RNA-SEQ FROM HUMAN EMBRYONIC STEM CELLS

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-09-30 | GSE86894 | GEO

ATAC-seq of bone marrow ILC2 lineages and Lung ILC2 steady state

Project description:ATAC-seq were performed for bone marrow ILC2 lineages and lung ILC2 of C57BL/6 mice and G3SEKO mice.

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RORa enforces stability of the T-helper-17 cell effector program

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-25 | GSE163342 | GEO

Minotaur is critical for primary piRNA biogenesis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-04-27 | E-GEOD-46424 | biostudies-arrayexpress

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