The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential

• Published in: Nature immunology Vol. 13; no. 4; pp. 412 - 419
• Main 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-04-2012; Nature Publishing Group
• Subjects: 631/250/1619/554; 631/250/1620/1840; 631/250/232; Animals; B cells; B-Lymphocytes - cytology; Basic Medicine; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell and Molecular Biology; Cell Lineage - immunology; Cell Separation; Cell- och molekylärbiologi; Development Biology; Embryology and Organogenesis; Flow Cytometry; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Immunology; Infectious Diseases; Life Sciences; Lymphocytes; Lymphoid Progenitor Cells - cytology; Lymphoid Progenitor Cells - immunology; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myeloid Cells - cytology; Oligonucleotide Array Sequence Analysis; Physiological aspects; Precursor Cells, B-Lymphoid - cytology; Real-Time Polymerase Chain Reaction; Stem cells; T cells; T-Lymphocytes - cytology; Thymus; Thymus Gland - cytology; United Kingdom
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/ni.2255

The commitment stage at which progenitors seed the thymus remains unclear. Jacobsen and colleagues show that the earliest progenitors in the neonatal thymus have combined myeloid, T lymphocyte and B lymphocyte potential but not megakaryocyte-erythroid potential.
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.