Title | Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Luis TC, Luc S, Mizukami T, Boukarabila H, Thongjuea S, Woll PS, Azzoni E, Giustacchini A, Lutteropp M, Bouriez-Jones T, Vaidya H, Mead AJ, Atkinson D, Böiers C, Carrelha J, Macaulay IC, Patient R, Geissmann F, Nerlov C, Sandberg R, de Bruijn MFTR, C Blackburn C, Godin I, Jacobsen SEirik W |
Journal | Nat Immunol |
Volume | 17 |
Issue | 12 |
Pagination | 1424-1435 |
Date Published | 2016 Dec |
ISSN | 1529-2916 |
Keywords | Animals, Cell Differentiation, Cell Lineage, Cell Movement, Cells, Cultured, Fetus, Gene Expression Regulation, Developmental, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Lymphoid Progenitor Cells, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myeloid Progenitor Cells, Receptors, Notch, Signal Transduction, T-Lymphocytes, Thymus Gland |
Abstract | The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors. Instead, single-cell molecular and functional analysis demonstrated that most fetal T-IPs expressed genes of and had the potential to develop into lymphoid as well as myeloid components of the immune system. Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs. |
DOI | 10.1038/ni.3576 |
Alternate Journal | Nat. Immunol. |
PubMed ID | 27695000 |
PubMed Central ID | PMC5172420 |
Grant List | MR/M00919X/1 / / Medical Research Council / United Kingdom MC_UU_12009/8 / / Medical Research Council / United Kingdom MC_U137981013 / / Medical Research Council / United Kingdom P30 CA008748 / CA / NCI NIH HHS / United States G0701761 / / Medical Research Council / United Kingdom MR/L006340/1 / / Medical Research Council / United Kingdom G0801073 / / Medical Research Council / United Kingdom MC_UU_12009/5 / / Medical Research Council / United Kingdom G0501838 / / Medical Research Council / United Kingdom MC_UU_12009/7 / / Medical Research Council / United Kingdom G0900892 / / Medical Research Council / United Kingdom |