Format

Send to

Choose Destination
Immunity. 2019 Jul 16;51(1):185-197.e6. doi: 10.1016/j.immuni.2019.06.001. Epub 2019 Jul 2.

Characterization of Transcriptional Regulatory Networks that Promote and Restrict Identities and Functions of Intestinal Innate Lymphoid Cells.

Author information

1
The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
2
Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
3
Departments of Biology and Computer Science, New York University, NY 10003, USA.
4
Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
5
The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute. Electronic address: dan.littman@med.nyu.edu.
6
Departments of Biology and Computer Science, New York University, NY 10003, USA; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA. Electronic address: bonneau@nyu.edu.
7
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Divisions of Immunobiology and Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Abstract

Innate lymphoid cells (ILCs) promote tissue homeostasis and immune defense but also contribute to inflammatory diseases. ILCs exhibit phenotypic and functional plasticity in response to environmental stimuli, yet the transcriptional regulatory networks (TRNs) that control ILC function are largely unknown. Here, we integrate gene expression and chromatin accessibility data to infer regulatory interactions between transcription factors (TFs) and genes within intestinal type 1, 2, and 3 ILC subsets. We predicted the "core" TFs driving ILC identities, organized TFs into cooperative modules controlling distinct gene programs, and validated roles for c-MAF and BCL6 as regulators affecting type 1 and type 3 ILC lineages. The ILC network revealed alternative-lineage-gene repression, a mechanism that may contribute to reported plasticity between ILC subsets. By connecting TFs to genes, the TRNs suggest means to selectively regulate ILC effector functions, while our network approach is broadly applicable to identifying regulators in other in vivo cell populations.

KEYWORDS:

ATAC-seq; Inferelator; gene regulation; lineage commitment; lymphocyte development

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center