Leading science, pioneering therapies
CRM Publications

Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.

TitleInitial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
Publication TypeJournal Article
Year of Publication2016
AuthorsLuis 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
JournalNat Immunol
Volume17
Issue12
Pagination1424-1435
Date Published2016 Dec
ISSN1529-2916
KeywordsAnimals, 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.

DOI10.1038/ni.3576
Alternate JournalNat. Immunol.
PubMed ID27695000
PubMed Central IDPMC5172420
Grant ListMR/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
Publication institute
CRM