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Published March 2021 | Published
Journal Article Open

Single-cell insights into the hematopoietic generation of T-lymphocyte precursors in mouse and human

Abstract

T-Cell development is a major branch of lymphoid development and a key output of hematopoiesis, especially in early life, but the molecular requirements for T-cell potential have remained obscure. Considerable advances have now been made toward solving this problem through single-cell transcriptome studies, interfaced with in vitro differentiation assays that monitor potential efficiently at the single-cell level. This review focuses on a series of recent reports studying mouse and human early T-cell precursors, both in the developing fetus and in stringently purified postnatal samples of intrathymic and prethymic T-lineage precursors. Cross-comparison of results reveals a robustly conserved core program in mouse and human, but with some informative and provocative variations between species and between ontogenic states. Repeated findings are the multipotent progenitor regulatory signature of thymus-seeding cells and the proximity of the T-cell program to dendritic cell programs, especially to plasmacytoid dendritic cells in humans.

Additional Information

© 2021 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 15 November 2020, Revised 23 December 2020, Accepted 24 December 2020, Available online 14 January 2021. The author thanks Ido Amit, Avinash Bhandoola, Gay Crooks, Ana Cumano, Kenneth Dorshkind, Berthold Göttgens, Muzlifah Haniffa, Andreas Krueger, Chintan Parekh, Hans-Reimer Rodewald, Tom Taghon, Sarah Teichmann, and Wen Zhou for sharing insightful discussions about work before it was published and about general principles of the field. Relevant support for work in the author's laboratory was obtained from U.S. Public Health Service Grants R01HL119102, R01HD076915, and R01HD100039, with support for EVR from the Albert Billings Ruddock Professorship of Biology. Conflict of interest disclosure: EVR is a member of the Scientific Advisory Board of Century Therapeutics and has consulted for A2 Biotherapeutics.

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