Published in

Rockefeller University Press, Journal of Experimental Medicine, 2(218), 2020

DOI: 10.1084/jem.20200487

Links

Tools

Export citation

Search in Google Scholar

Multi-transcription factor reporter mice delineate early precursors to the ILC and LTi lineages

Journal article published in 2020 by Darshan N. Kasal ORCID, Albert Bendelac ORCID
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

Full text: Unavailable

Green circle
Preprint: archiving allowed
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Data provided by SHERPA/RoMEO

Abstract

Transcription factor (TF) reporter mice have proved integral to the characterization of murine innate lymphoid cell (ILC) development and function. Here, we implemented a CRISPR/Cas9-generated combinatorial reporter approach for the simultaneous resolution of several key TFs throughout ILC development in both the fetal liver and adult bone marrow. We demonstrate that the Tcf7-expressing early innate lymphoid precursor (EILP) and the common helper ILC precursor (CHILP) both contain a heterogeneous mixture of specified ILC and lymphoid tissue inducer (LTi) precursors with restricted lineage potential rather than a shared precursor. Moreover, the earliest specified precursor to the LTi lineage was identified upstream of these populations, before Tcf7 expression. These findings match dynamic changes in chromatin accessibility associated with the expression of key TFs (i.e., GATA3 and RORγ(t)), highlighting the distinct origins of ILC and LTi lineages at the epigenetic and functional levels, and provide a revised map for ILC development.