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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.

Original publication

DOI

10.1038/ni.2255

Type

Journal article

Journal

Nature immunology

Publication Date

19/02/2012

Volume

13

Pages

412 - 419

Addresses

Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.

Keywords

Thymus Gland, B-Lymphocytes, T-Lymphocytes, Hematopoietic Stem Cells, Myeloid Cells, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Oligonucleotide Array Sequence Analysis, Flow Cytometry, Cell Separation, Cell Lineage, Precursor Cells, B-Lymphoid, Lymphoid Progenitor Cells, Real-Time Polymerase Chain Reaction