Single-cell multi-omic analysis of thymocyte development reveals NFAT as a driver of CD4/CD8 lineage commitment

Zoë Steier, Laura L. McIntyre, Lydia K. Lutes, Tse-Shun Huang, Ellen A. Robey, Nir Yosef, Aaron Streets

פרסום מחקרי: פרסום בכתב עתמאמר

תקציר

CD4 and CD8 T cells play critical roles in the mammalian immune system. While their development within the thymus from the CD4+CD8+ stage has been widely studied as a model of lineage commitment, the underlying mechanism remains unclear. To deconstruct this process, we apply CITE-seq, measuring the transcriptome and over 100 surface proteins in thymocytes from wild-type and lineage-restricted mice. We jointly analyze the paired measurements to build a comprehensive timeline of RNA and protein expression in each lineage, supporting a sequential model of lineage determination in which both lineages go through an initial phase of CD4 lineage audition, which is followed by divergence and specification of CD8 lineage cells. We identify early differences implicating T cell receptor signaling via calcineurin-NFAT in driving CD4 lineage commitment. Pharmacological inhibition validates the requirement of calcineurin- NFAT for CD4, but not CD8, lineage development, providing insight into the CD4/CD8 commitment mechanism.
שפה מקוריתאנגלית
מספר עמודים54
כתב עתBioRxiv
סטטוס פרסוםבהכנה - 13 יולי 2021
פורסם באופן חיצוניכן

טביעת אצבע

להלן מוצגים תחומי המחקר של הפרסום 'Single-cell multi-omic analysis of thymocyte development reveals NFAT as a driver of CD4/CD8 lineage commitment'. יחד הם יוצרים טביעת אצבע ייחודית.

פורמט ציטוט ביבליוגרפי