Sidinh Luc,
Tiago C Luis,
Hanane Boukarabila,
Iain C Macaulay,
Natalija Buza-Vidas,
Tiphaine Bouriez-Jones,
Michael Lutteropp,
Petter S Woll,
Stephen J Loughran,
Adam J Mead, [......],
Alison Farley, Alejandra Sanjuan-Pla,
Cintia Carella,
Roger Patient,
Marella de Bruijn,
Tariq Enver,
Claus Nerlov,
Clare Blackburn,
Isabelle Godin,
Sten Eirik W Jacobsen
[show abstract]
[hide abstract]
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.
Nature Immunology 02/2012; 13(4):412-9. · 26.01 Impact Factor