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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Tiago C. Luis
  • Sidinh Luc
  • Takuo Mizukami
  • Hanane Boukarabila
  • Supat Thongjuea
  • Petter S. Woll
  • Emanuele Azzoni
  • Alice Giustacchini
  • Michael Lutteropp
  • Tiphaine Bouriez-Jones
  • Harsh Vaidya
  • Adam J. Mead
  • Deborah Atkinson
  • Joana Carrelha
  • Iain C. MacAulay
  • Roger Patient
  • Frederic Geissmann
  • Claus Nerlov
  • Rickard Sandberg
  • Marella F T R De Bruijn
  • C. Clare Blackburn
  • Isabelle Godin
  • Sten Eirik W Jacobsen
Organisations
External organisations
  • University of Oxford
  • Boston Children's Hospital
  • University of Edinburgh
  • Memorial Sloan-Kettering Cancer Center
  • Karolinska Institutet
  • Karolinska University Hospital
  • King's College London
  • University of Paris-Sud
  • Institut Gustave Roussy
  • National Institute for Health and Medical Research, France
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)1424-1435
Number of pages12
JournalNature Immunology
Volume17
Issue number12
Publication statusPublished - 2016 Dec 1
Publication categoryResearch
Peer-reviewedYes