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

Christelle Harly; Devin Kenney; Gang Ren; Binbin Lai; Tobias Raabe; Qi Yang; Margaret C. Cam; Hai Hui Xue; Keji Zhao; Avinash Bhandoola

doi:10.1038/s41590-019-0445-7

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

Christelle Harly
, Devin Kenney
, Gang Ren
, Binbin Lai
, Tobias Raabe
, Qi Yang
, Margaret C. Cam
, Hai Hui Xue
, Keji Zhao
, Avinash Bhandoola

Center for Discovery and Innovation

National Institutes of Health
Université d'Angers
LabEx IGO ‘Immunotherapy
University of Pennsylvania
Albany Medical College

Research output: Contribution to journal › Article › peer-review

106 Scopus citations

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.

Original language	English
Pages (from-to)	1150-1160
Number of pages	11
Journal	Nature Immunology
Volume	20
Issue number	9
DOIs	https://doi.org/10.1038/s41590-019-0445-7
State	Published - 1 Sep 2019

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title = "The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage",

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{\textendash}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 {\textquoteleft}specified EILPs{\textquoteright} and {\textquoteleft}committed EILPs{\textquoteright}. 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.",

author = "Christelle Harly and Devin Kenney and Gang Ren and Binbin Lai and Tobias Raabe and Qi Yang and Cam, \{Margaret C.\} and Xue, \{Hai Hui\} and Keji Zhao and Avinash Bhandoola",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = sep,

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doi = "10.1038/s41590-019-0445-7",

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T1 - The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage

AU - Harly, Christelle

AU - Kenney, Devin

AU - Ren, Gang

AU - Lai, Binbin

AU - Raabe, Tobias

AU - Yang, Qi

AU - Cam, Margaret C.

AU - Xue, Hai Hui

AU - Zhao, Keji

AU - Bhandoola, Avinash

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41590-019-0445-7

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SN - 1529-2908

VL - 20

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JO - Nature Immunology

JF - Nature Immunology

IS - 9

ER -

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

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