Servicenavigation

Project Details

Back

Projekt Print View

Unveiling differentiation trajectories of T lymphocytes with single cell resolution

Subject Area Cell Biology
Bioinformatics and Theoretical Biology
Term from 2017 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 371991985
 
Final Report Year 2023

Final Report Abstract

In the project “Unveiling differenBaBon trajectories of T lymphocytes with single cell resoluBon” we proposed to use single-cell RNA-sequencing for the characterizaBon of lymphocyte differenBaBon in the bone marrow and of bone marrow-derived progenitors into different types of T cells in the thymus. In the first part of this project, we focused on murine hematopoieBc progenitors isolated from the bone marrow of adult mice which we profiled by a customized single-cell RNA-sequencing protocol. We developed FateID, a computaBonal algorithm for the predicBon of cell fate probabiliBes of each progenitor cell, and discovered a lymphoid progenitor populaBon giving rise to both B cells and plasmacytoid dendriBc cells (pDCs). We could validate this populaBon by in vitro culture experiments and established a lymphoid origin of pDCs, which were formerly believed to be of myeloid origin. This finding was confirmed by independent studies from other research groups and is now well accepted in the community. In the second part of the project we invesBgated T cell differenBaBon in the murine thymus by reconstrucBng high-resoluBon differenBaBon trajectories inferred from single-cell RNA-sequencing data, which we generated for thymic T cell progenitors. Our analysis confirmed the convenBonal model of abT cell differenBaBon, while we could reconstruct a novel differenBaBon trajectory of T cell progenitors towards different subtypes of gdT cells in the thymus of adult and neonatal mice. We discovered the transcripBon factor c-Maf as a novel key regulator of Il17-producing gdT cell differenBaBon and predicted a temporal hierarchy of the transcripBon factors Sox13, c-Maf, and Rorc governing differenBaBon of Il17-producing gdT cells, which we validated by single-cell RNA-sequencing of gdT cells isolated from geneBc knockout mouse model of the three individual factors. Hence, in this project we could acquire a deeper understanding of the underpinnings of gdT cell differenBaBon. In summary, we could achieve the goals of the proposed research and publish our results in two high-impact papers.

Publications

 
 

Additional Information

© 2026 DFG Disclaimer / Copyright / Privacy Policy

Textvergrößerung und Kontrastanpassung