1. Multi-transcription factor reporter mice delineate early precursors to the ILC and LTi lineages.
- Author
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Kasal DN and Bendelac A
- Subjects
- Animals, Bone Marrow immunology, Cell Differentiation immunology, Chromatin immunology, Gene Expression Regulation immunology, Immunity, Innate immunology, Mice, Mice, Inbred C57BL, T-Lymphocytes, Helper-Inducer immunology, Cell Lineage immunology, Lymphocytes immunology, Lymphoid Tissue immunology, Transcription Factors immunology
- 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., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Kasal and Bendelac.)
- Published
- 2021
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