PT  - JOURNAL ARTICLE
AU  - Marieke Lavaert
AU  - Kai Ling Liang
AU  - Niels Vandamme
AU  - Jong-Eun Park
AU  - Juliette Roels
AU  - Monica S. Kowalczyk
AU  - Bo Li
AU  - Orr Ashenberg
AU  - Marcin Tabaka
AU  - Danielle Dionne
AU  - Timothy L. Tickle
AU  - Michal Slyper
AU  - Orit Rozenblatt-Rosen
AU  - Bart Vandekerckhove
AU  - Georges Leclercq
AU  - Aviv Regev
AU  - Pieter Van Vlierberghe
AU  - Martin Guilliams
AU  - Sarah A. Teichmann
AU  - Yvan Saeys
AU  - Tom Taghon
TI  - Single cell profiling of immature human postnatal thymocytes resolves the complexity of intra-thymic lineage differentiation and thymus seeding precursors
AID  - 10.1101/2020.04.07.007237
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.07.007237
4099  - http://biorxiv.org/content/early/2020/04/08/2020.04.07.007237.short
4100  - http://biorxiv.org/content/early/2020/04/08/2020.04.07.007237.full
AB  - 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.