The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage

Nat Immunol. 2019 Sep;20(9):1150-1160. doi: 10.1038/s41590-019-0445-7. Epub 2019 Jul 29.

Abstract

Innate lymphoid cells (ILCs) play important functions in immunity and tissue homeostasis, but their development is poorly understood. Through the use of single-cell approaches, we examined the transcriptional and functional heterogeneity of ILC progenitors, and studied the precursor-product relationships that link the subsets identified. This analysis identified two successive stages of ILC development within T cell factor 1-positive (TCF-1+) early innate lymphoid progenitors (EILPs), which we named 'specified EILPs' and 'committed EILPs'. Specified EILPs generated dendritic cells, whereas this potential was greatly decreased in committed EILPs. TCF-1 was dispensable for the generation of specified EILPs, but required for the generation of committed EILPs. TCF-1 used a pre-existing regulatory landscape established in upstream lymphoid precursors to bind chromatin in EILPs. Our results provide insight into the mechanisms by which TCF-1 promotes developmental progression of ILC precursors, while constraining their dendritic cell lineage potential and enforcing commitment to ILC fate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Lineage / immunology*
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Gene Expression Regulation / genetics
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / immunology*
  • Lymphoid Progenitor Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / cytology*
  • Transcription, Genetic / genetics

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse