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Nat Immunol. 2016 Mar;17(3):269-76. doi: 10.1038/ni.3344. Epub 2016 Jan 18.

Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.

Author information

1
Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
2
Department of Pathology, University of Chicago, Chicago, Illinois, USA.
3
Institut Pasteur, Immunology Department, Lymphopoiesis Unit, Inserm U668, University Paris Diderot, Paris, France.
4
Institute of Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA.
5
Department of Chemistry, University of Chicago, Chicago, Illinois, USA.

Abstract

The precise lineage relationship between innate lymphoid cells (ILCs) and lymphoid tissue-inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and found that its bifurcation was marked by differential induction of the transcription factors PLZF and TCF1. Acquisition of individual effector programs specific to the ILC subsets ILC1, ILC2 and ILC3 was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns, whereas, in contrast, the development of LTi cells did not go through multilineage priming. Our findings provide insight into the divergent mechanisms of the differentiation of the ILC lineage and LTi cell lineage and establish a high-resolution 'blueprint' of their development.

PMID:
26779601
PMCID:
PMC4755916
DOI:
10.1038/ni.3344
[Indexed for MEDLINE]
Free PMC Article

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