Back

Single cell profiling of immature human postnatal thymocytes resolves the complexity of intra-thymic lineage differentiation and thymus seeding precursors.

Lavaert, M.; Liang, K. L.; Vandamme, N.; Park, J.-E.; Roels, J.; Kowalczyk, M. S.; Li, B.; Ashenberg, O.; Tabaka, M.; Dionne, D.; Tickle, T. L.; Slyper, M.; Rozenblatt-Rosen, O.; Vandekerckhove, B.; Leclercq, G.; Regev, A.; Van Vlierberghe, P.; Guilliams, M.; Teichmann, S. A.; Saeys, Y.; Taghon, T.

2020-04-08 immunology
10.1101/2020.04.07.007237 bioRxiv
Show abstract

During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone marrow derived hematopoietic progenitors that migrate through the bloodstream. In human, the nature of these thymus immigrants has remained unclear. Here, we employ single-cell RNA sequencing on approximately 70.000 CD34+ thymocytes to unravel the heterogeneity of the human immature postnatal thymocytes. Integration of bone marrow and peripheral blood precursors datasets identifies several putative thymus seeding precursors that display heterogeneity for currently used surface markers as revealed by CITEseq. Besides T cell precursors, we discover branches of intrathymic developing dendritic cells with predominantly plasmacytoid DCs. Trough trajectory inference, we delineate the transcriptional dynamics underlying early human T-lineage development from which we predict transcription factor modules that drive stage-specific steps of human T cell development. Thus, our work resolves the heterogeneity of thymus seeding precursors in human and reveals the molecular mechanisms that drive their in vivo cell fate.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.