Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes
Marieke Lavaert, Kai Ling Liang, Niels Vandamme, Jong-Eun Park, Juliette Roels, Monica S. Kowalczyk, Bo Li, Orr Ashenberg, Marcin Tabaka, Danielle Dionne, Timothy L. Tickle, Michal Slyper, Orit Rozenblatt-Rosen, Bart Vandekerckhove, Georges Leclercq, Aviv Regev, Pieter Van Vlierberghe, Martin Guilliams, Sarah A. Teichmann, Yvan Saeys, Tom Taghon
Abstract
During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone-marrow-derived hematopoietic progenitors that migrate through the bloodstream. The current understanding of the nature of thymic immigrants is largely based on data from pre-clinical models. Here, we employed single-cell RNA sequencing (scRNA-seq) to examine the immature postnatal thymocyte population in humans. Integration of bone marrow and peripheral blood precursor datasets identified two putative thymus seeding progenitors that varied in expression of CD7; CD10; and the homing receptors CCR7, CCR9, and ITGB7. Whereas both precursors supported T cell development, only one contributed to intrathymic dendritic cell (DC) differentiation, predominantly of plasmacytoid dendritic cells. Trajectory inference delineated the transcriptional dynamics underlying early human T lineage development, enabling prediction of transcription factor (TF) modules that drive stage-specific steps of human T cell development. This comprehensive dataset defines the expression signature of immature human thymocytes and provides a resource for the further study of human thymopoiesis.
Datasets
1. Single-Cell Transcriptome Profiling of Immature Human Thymocytes
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Source data
https://cellxgene.cziscience.com/collections/83ed3be8-4cb9-43e6-9aaa-3fbbf5d1bd3a
Alias names
GSE144870, PMID32304633
Cite this study
Lavaert, M., Liang, K.L., Vandamme, N., Park, J.E., Roels, J., Kowalczyk, M.S., Li, B., Ashenberg, O., Tabaka, M., Dionne, D. and Tickle, T.L., 2020. Integrated scRNA-Seq identifies human postnatal thymus seeding progenitors and regulatory dynamics of differentiating immature thymocytes. Immunity, 52(6), pp.1088-1104. https://doi.org/10.1016/j.immuni.2020.03.019