Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo

Jennifer Easterbrook; Stanislav Rybtsov; Sabrina Gordon-Keylock; Andrejs Ivanovs; Samir Taoudi; Richard A Anderson; Alexander Medvinsky

doi:10.1016/j.stemcr.2019.03.003

Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo

Stem Cell Reports. 2019 May 14;12(5):1056-1068. doi: 10.1016/j.stemcr.2019.03.003. Epub 2019 Apr 4.

Authors

Jennifer Easterbrook¹, Stanislav Rybtsov¹, Sabrina Gordon-Keylock¹, Andrejs Ivanovs², Samir Taoudi³, Richard A Anderson⁴, Alexander Medvinsky⁵

Affiliations

¹ Ontogeny of Haematopoietic Stem Cells Group, Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
² Ontogeny of Haematopoietic Stem Cells Group, Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK; Institute of Anatomy and Anthropology, Riga Stradiņš University, Riga 1007, Latvia.
³ Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052 Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia; Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
⁴ MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
⁵ Ontogeny of Haematopoietic Stem Cells Group, Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK. Electronic address: a.medvinsky@ed.ac.uk.

Abstract

Definitive hematopoietic stem cells (HSCs) first emerge in the aorta-gonad-mesonephros (AGM) region in both mice and humans. An ex vivo culture approach has enabled recapitulation and analysis of murine HSC development. Knowledge of early human HSC development is hampered by scarcity of tissue: analysis of both CFU-C and HSC development in the human embryo is limited. Here, we characterized the spatial distribution and temporal kinetics of CFU-C development within early human embryonic tissues. We then sought to adapt the murine ex vivo culture system to recapitulate human HSC development. We show robust expansion of CFU-Cs and maintenance, but no significant expansion, of human HSCs in culture. Furthermore, we demonstrate that HSCs emerge predominantly in the middle section of the dorsal aorta in our culture system. We conclude that there are important differences between early mouse and human hematopoiesis, which currently hinder the quest to recapitulate human HSC development ex vivo.

Keywords: fetal liver; hematopoietic progenitors; hematopoietic stem cells; human embryo; yolk sac.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta / cytology*
Cell Proliferation / physiology
Cells, Cultured
Colony-Forming Units Assay
Embryo, Mammalian / cytology*
Embryo, Mammalian / embryology
Gonads / cytology
Hematopoiesis / physiology
Hematopoietic Stem Cell Transplantation / methods
Hematopoietic Stem Cells / cytology*
Heterografts
Humans
Interleukin Receptor Common gamma Subunit / deficiency
Interleukin Receptor Common gamma Subunit / genetics
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Spatio-Temporal Analysis*
Stem Cells / cytology*

Substances

Il2rg protein, mouse
Interleukin Receptor Common gamma Subunit

Abstract

Publication types

MeSH terms

Substances

Grants and funding