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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.

Original publication

DOI

10.1038/ni.3576

Type

Journal article

Journal

Nature immunology

Publication Date

12/2016

Volume

17

Pages

1424 - 1435

Addresses

Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.

Keywords

Thymus Gland, T-Lymphocytes, Myeloid Progenitor Cells, Cells, Cultured, Fetus, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Signal Transduction, Cell Differentiation, Cell Movement, Gene Expression Regulation, Developmental, Cell Lineage, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Receptors, Notch, Lymphoid Progenitor Cells