Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver.
One day prior to mass emergence of haematopoietic stem cells (HSCs) in the foetal liver at E12.5, the embryo contains only a few definitive HSCs. It is thought that the burst of HSC activity in the foetal liver is underpinned by rapid maturation of immature embryonic precursors of definitive HSCs, termed pre-HSCs. However, because pre-HSCs are not detectable by direct transplantations into adult irradiated recipients, the size and growth of this population, which represents the embryonic rudiment of the adult haematopoietic system, remains uncertain. Using a novel quantitative assay, we demonstrate that from E9.5 the pre-HSC pool undergoes dramatic growth in the aorta-gonad-mesonephros region and by E11.5 reaches the size that matches the number of definitive HSCs in the E12.5 foetal liver. Thus, this study provides for the first time a quantitative basis for our understanding of how the large population of definitive HSCs emerges in the foetal liver.
Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter, 5 Little France Drive, Edinburgh E16 4UU, UK.
Stanislav
http://orcid.org/0000-0001-7786-1878
S
Rybtsov
Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter, 5 Little France Drive, Edinburgh E16 4UU, UK.
Andrejs
A
Ivanovs
Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter, 5 Little France Drive, Edinburgh E16 4UU, UK.
Suling
S
Zhao
Institute for Stem Cell Research, Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, SCRM Bioquarter, 5 Little France Drive, Edinburgh E16 4UU, UK A.Medvinsky@ed.ac.uk.
Alexander
A
Medvinsky
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
AGM region; Embryo; HSC; Mouse; Pre-HSC