Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development
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 d...
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| Vydáno v: | Cell stem cell Ročník 27; číslo 5; s. 822 |
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| Hlavní autoři: | , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
05.11.2020
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| ISSN: | 1875-9777, 1875-9777 |
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Author | Chandra, Tamir Tamagno, Sara Medvinsky, Alexander Gordon-Keylock, Sabrina Rybtsov, Stanislav Binagui-Casas, Anahi Crosse, Edie I Nnadi, Nneka C Webb, David J Anderson, Richard A Kirschner, Kristina Felchle, Hannah Rossi, Fiona |
| Author_xml | – sequence: 1 givenname: Edie I surname: Crosse fullname: Crosse, Edie I organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 2 givenname: Sabrina surname: Gordon-Keylock fullname: Gordon-Keylock, Sabrina organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 3 givenname: Stanislav surname: Rybtsov fullname: Rybtsov, Stanislav organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 4 givenname: Anahi surname: Binagui-Casas fullname: Binagui-Casas, Anahi organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 5 givenname: Hannah surname: Felchle fullname: Felchle, Hannah organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 6 givenname: Nneka C surname: Nnadi fullname: Nnadi, Nneka C organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 7 givenname: Kristina surname: Kirschner fullname: Kirschner, Kristina organization: Institute of Cancer Sciences, University of Glasgow, Bearsden G61 1QH, UK – sequence: 8 givenname: Tamir surname: Chandra fullname: Chandra, Tamir organization: MRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, UK – sequence: 9 givenname: Sara surname: Tamagno fullname: Tamagno, Sara organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 10 givenname: David J surname: Webb fullname: Webb, David J organization: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK – sequence: 11 givenname: Fiona surname: Rossi fullname: Rossi, Fiona organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK – sequence: 12 givenname: Richard A surname: Anderson fullname: Anderson, Richard A organization: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ UK – sequence: 13 givenname: Alexander surname: Medvinsky fullname: Medvinsky, Alexander email: a.medvinsky@ed.ac.uk organization: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK. Electronic address: a.medvinsky@ed.ac.uk |
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| Keywords | single cell transcriptome endothelin hematopoiesis AGM region HSC embryo spatial transcriptome |
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| Title | Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development |
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