Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.
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.
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Tiago C
TC
Luis
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.|Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, Klinikgatan 26, 221 84, Lund, Sweden.|MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Sidinh
S
Luc
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Takuo
T
Mizukami
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Hanane
H
Boukarabila
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.|MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Supat
S
Thongjuea
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Petter S
PS
Woll
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Emanuele
E
Azzoni
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Alice
A
Giustacchini
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.|MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Michael
M
Lutteropp
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Tiphaine
T
Bouriez-Jones
Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, EH16 4UU Edinburgh, UK.
Harsh
H
Vaidya
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Adam J
AJ
Mead
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Deborah
D
Atkinson
Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
Charlotta
C
Böiers
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Joana
J
Carrelha
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.
Iain C
IC
Macaulay
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Roger
R
Patient
King's College London, Great Maze Pond, SE1 1UL London, UK.|Memorial Sloan Kettering Cancer Center, 417 East 68(th) Street, New York, NY 10065, USA.
Frederic
F
Geissmann
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Claus
C
Nerlov
Department of Cell and Molecular Biology, Karolinska Institutet and Ludwig Institute for Cancer Research, 171 77 Stockholm, Sweden.
Rickard
R
Sandberg
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Marella F T R
MFTR
de Bruijn
Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, EH16 4UU Edinburgh, UK.
C Clare
CC
Blackburn
Institut National de la Santé et de la Recherche Médicale U1170; Univ Paris-Sud, Université Paris-Saclay; Gustave Roussy, 114, rue Edouard Vaillant; Villejuif, F-94805, France.
Isabelle
I
Godin
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, United Kingdom.|MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.|Department of Cell and Molecular Biology, Wallenberg Institute for Regenerative Medicine and Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, 171 77 Stockholm, Sweden.
Sten Eirik W
SEW
Jacobsen
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*
D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch
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