Work

Single-cell multi-omic analysis of thymocyte development reveals drivers of CD4/CD8 lineage commitment

Year: 2021

Type: preprint

Abstract: The development of CD4 and CD8 T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-MHCI/II by the T cell antigen receptor (TCR) determines the lineage choice, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. We applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and lineage-restricted mice to generate a comprehensive timeline of cell state for each lineage. These analyses revealed a sequential process whereby all thymocytes initiate CD4 lineage differentiation during an initial wave of TCR signaling, followed by a second TCR signaling wave that coincides with CD8 lineage specification. CITE-seq and pharmaceutical inhibition experiments implicate a TCR/calcineurin/NFAT/GATA3 axis in driving the CD4 fate. Overall, our data suggest that multiple redundant mechanisms contribute to the accuracy and efficiency of the lineage choice.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/2021.07.12.452119

Authors: Zoë Steier, Dominik A. Aylard, Laura L. McIntyre, Isabel Baldwin, Esther Jeong Yoon Kim, Lydia K. Lutes, Can Ergen, Tse-Shun Huang, Ellen A. Robey, Nir Yosef, Aaron Streets

Institutions: University of California, San Francisco, Centre de Bio-Informatique, University of California, Berkeley, BioLegend (United States), Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Chan Zuckerberg Biohub San Francisco, Massachusetts Institute of Technology

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

OpenAlex ID: W3182678173

Cites: 108

Cited by: 3

Related to: 10