Edie I Crosse, Sabrina Gordon-Keylock, Stanislav Rybtsov, Anahi Binagui-Casas, Hannah Felchle, Nneka C Nnadi, Kristina Kirschner, Tamir Chandra, Sara Tamagno, David J Webb, Fiona Rossi, Richard A Anderson, Alexander Medvinsky
Author Information
Edie I Crosse: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Sabrina Gordon-Keylock: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Stanislav Rybtsov: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Anahi Binagui-Casas: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Hannah Felchle: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Nneka C Nnadi: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Kristina Kirschner: Institute of Cancer Sciences, University of Glasgow, Bearsden G61 1QH, UK.
Tamir Chandra: MRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, UK.
Sara Tamagno: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
David J Webb: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Fiona Rossi: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Richard A Anderson: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ UK.
Alexander Medvinsky: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK. Electronic address: a.medvinsky@ed.ac.uk.
Hematopoietic stem cells (HSCs) first emerge in the embryonic aorta-gonad-mesonephros (AGM) region. Studies of model organisms defined intersecting signaling pathways that converge to promote HSC emergence predominantly in the ventral domain of the dorsal aorta. Much less is known about mechanisms driving HSC development in humans. Here, to identify secreted signals underlying human HSC development, we combined spatial transcriptomics analysis of dorsoventral polarized signaling in the aorta with gene expression profiling of sorted cell populations and single cells. Our analysis revealed a subset of aortic endothelial cells with a downregulated arterial signature and a predicted lineage relationship with the emerging HSC/progenitor population. Analysis of the ventrally polarized molecular landscape identified endothelin 1 as an important secreted regulator of human HSC development. The obtained gene expression datasets will inform future studies on mechanisms of HSC development in vivo and on generation of clinically relevant HSCs in vitro.
