Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells.
In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the embryonic lymphoid commitment process initiates earlier than previously appreciated, prior to emergence of definitive HSCs, through establishment of a previously unrecognized entirely immune-restricted and lymphoid-primed progenitor. Notably, this immune-restricted progenitor appears to first emerge in the yolk sac and contributes physiologically to the establishment of lymphoid and some myeloid components of the immune-system, establishing the lymphomyeloid lineage restriction process as an early and physiologically important lineage-commitment step in mammalian hematopoiesis.
Haematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden; Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
Charlotta
C
Böiers
Joana
J
Carrelha
Michael
M
Lutteropp
Sidinh
S
Luc
Joanna C A
JC
Green
Emanuele
E
Azzoni
Petter S
PS
Woll
Adam J
AJ
Mead
Anne
A
Hultquist
Gemma
G
Swiers
Elisa Gomez
EG
Perdiguero
Iain C
IC
Macaulay
Luca
L
Melchiori
Tiago C
TC
Luis
Shabnam
S
Kharazi
Tiphaine
T
Bouriez-Jones
Qiaolin
Q
Deng
Annica
A
Pontén
Deborah
D
Atkinson
Christina T
CT
Jensen
Ewa
E
Sitnicka
Frederic
F
Geissmann
Isabelle
I
Godin
Rickard
R
Sandberg
Marella F T R
MF
de Bruijn
Sten Eirik W
SE
Jacobsen
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D016133:Polymerase Chain Reaction