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The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential |
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| Authors: | Luc Sidinh Luis Tiago C Boukarabila Hanane Macaulay Iain C Buza-Vidas Natalija Bouriez-Jones Tiphaine Lutteropp Michael Woll Petter S Loughran Stephen J Mead Adam J Hultquist Anne Brown John Mizukami Takuo Matsuoka Sahoko Ferry Helen Anderson Kristina Duarte Sara Atkinson Deborah Soneji Shamit Domanski Aniela Farley Alison Sanjuan-Pla Alejandra Carella Cintia Patient Roger de Bruijn Marella Enver Tariq Nerlov Claus Blackburn Clare Godin Isabelle Jacobsen Sten Eirik W |
| Affiliation: | Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. |
| Abstract: | The stepwise commitment from hematopoietic stem cells in the bone marrow to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage-restricted progenitors. However, the commitment stage at which progenitors migrate from the bone marrow to the thymus remains unclear. Here we provide functional and molecular evidence at the single-cell level that the earliest progenitors in the neonatal thymus had combined granulocyte-monocyte, T lymphocyte and B lymphocyte lineage potential but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of candidate thymus-seeding progenitors in the bone marrow, which were closely related at the molecular level. Our findings establish the distinct lineage-restriction stage at which the T cell lineage-commitment process transits from the bone marrow to the remote thymus. |
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