Single-cell RNA transcriptomics identifies Hivep3 as essential in regulating the development of innate-like T lymphocytes

Krovi, S. H.; Zhang, J.; Michaels-Foster, M. J.; Brunetti, T.; Loh, L.; Scott-Browne, J.; Gapin, L.

doi:10.1101/2020.06.08.135129

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bioRxiv · 10.1101/2020.06.08.135129

Single-cell RNA transcriptomics identifies Hivep3 as essential in regulating the development of innate-like T lymphocytes

Krovi, S. H.·Zhang, J.·Michaels-Foster, M. J.·Brunetti, T.·Loh, L.·Scott-Browne, J.·Gapin, L.

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Abstract

Most T lymphocytes leave the thymus as naive cells with limited functionality. However, unique populations of T cells, commonly known as innate-like T cells, differentiate into functionally distinct effector subsets during thymic development under the influence of the transcription factor PLZF. Here, we profiled >10,000 differentiating thymic iNKT cells using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of their maturation, function, and fate decision in steady state. We identified Hivep3, a zinc finger transcription factor and adaptor protein, as a key factor that is expressed in early precursors and regulates the post-selection proliferative burst, differentiation and functions of iNKT cells. Importantly, we extended these results to other PLZF+ innate-like T cell populations, highlighting the unique and common requirement of Hivep3 to the development of all innate-like T cells.

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Krovi, S. H., Zhang, J., Michaels-Foster, M. J., Brunetti, T., Loh, L., Scott-Browne, J., Gapin, L.. 2020-06-09. Single-cell RNA transcriptomics identifies Hivep3 as essential in regulating the development of innate-like T lymphocytes. https://doi.org/10.1101/2020.06.08.135129

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