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Decoding human fetal liver haematopoiesis
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~140,000 liver and ~74,000 skin, kidney and yolk sac cells, we ide...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861135/ https://www.ncbi.nlm.nih.gov/pubmed/31597962 http://dx.doi.org/10.1038/s41586-019-1652-y |
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author | Popescu, Dorin-Mirel Botting, Rachel A. Stephenson, Emily Green, Kile Webb, Simone Jardine, Laura Calderbank, Emily F. Polanski, Krzysztof Goh, Issac Efremova, Mirjana Acres, Meghan Maunder, Daniel Vegh, Peter Gitton, Yorick Park, Jong-Eun Vento-Tormo, Roser Miao, Zhichao Dixon, David Rowell, Rachel McDonald, David Fletcher, James Poyner, Elizabeth Reynolds, Gary Mather, Michael Moldovan, Corina Mamanova, Lira Greig, Frankie Young, Matthew Meyer, Kerstin B. Lisgo, Steven Bacardit, Jaume Fuller, Andrew Millar, Ben Innes, Barbara Lindsay, Susan Stubbington, Michael J. T. Kowalczyk, Monika S. Li, Bo Ashenbrg, Orr Tabaka, Marcin Dionne, Danielle Tickle, Timothy L. Slyper, Michal Rozenblatt-Rosen, Orit Filby, Andrew Carey, Peter Villani, Alexandra-Chloe Roy, Anindita Regev, Aviv Chedotal, Alain Roberts, Irene Göttgens, Berthold Behjati, Sam Laurenti, Elisa Teichmann, Sarah A. Haniffa, Muzlifah |
author_facet | Popescu, Dorin-Mirel Botting, Rachel A. Stephenson, Emily Green, Kile Webb, Simone Jardine, Laura Calderbank, Emily F. Polanski, Krzysztof Goh, Issac Efremova, Mirjana Acres, Meghan Maunder, Daniel Vegh, Peter Gitton, Yorick Park, Jong-Eun Vento-Tormo, Roser Miao, Zhichao Dixon, David Rowell, Rachel McDonald, David Fletcher, James Poyner, Elizabeth Reynolds, Gary Mather, Michael Moldovan, Corina Mamanova, Lira Greig, Frankie Young, Matthew Meyer, Kerstin B. Lisgo, Steven Bacardit, Jaume Fuller, Andrew Millar, Ben Innes, Barbara Lindsay, Susan Stubbington, Michael J. T. Kowalczyk, Monika S. Li, Bo Ashenbrg, Orr Tabaka, Marcin Dionne, Danielle Tickle, Timothy L. Slyper, Michal Rozenblatt-Rosen, Orit Filby, Andrew Carey, Peter Villani, Alexandra-Chloe Roy, Anindita Regev, Aviv Chedotal, Alain Roberts, Irene Göttgens, Berthold Behjati, Sam Laurenti, Elisa Teichmann, Sarah A. Haniffa, Muzlifah |
author_sort | Popescu, Dorin-Mirel |
collection | PubMed |
description | Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~140,000 liver and ~74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the impact of tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, NK and ILC precursors in the yolk sac. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for harnessing the therapeutic potential of HSC/MPPs. |
format | Online Article Text |
id | pubmed-6861135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68611352020-04-09 Decoding human fetal liver haematopoiesis Popescu, Dorin-Mirel Botting, Rachel A. Stephenson, Emily Green, Kile Webb, Simone Jardine, Laura Calderbank, Emily F. Polanski, Krzysztof Goh, Issac Efremova, Mirjana Acres, Meghan Maunder, Daniel Vegh, Peter Gitton, Yorick Park, Jong-Eun Vento-Tormo, Roser Miao, Zhichao Dixon, David Rowell, Rachel McDonald, David Fletcher, James Poyner, Elizabeth Reynolds, Gary Mather, Michael Moldovan, Corina Mamanova, Lira Greig, Frankie Young, Matthew Meyer, Kerstin B. Lisgo, Steven Bacardit, Jaume Fuller, Andrew Millar, Ben Innes, Barbara Lindsay, Susan Stubbington, Michael J. T. Kowalczyk, Monika S. Li, Bo Ashenbrg, Orr Tabaka, Marcin Dionne, Danielle Tickle, Timothy L. Slyper, Michal Rozenblatt-Rosen, Orit Filby, Andrew Carey, Peter Villani, Alexandra-Chloe Roy, Anindita Regev, Aviv Chedotal, Alain Roberts, Irene Göttgens, Berthold Behjati, Sam Laurenti, Elisa Teichmann, Sarah A. Haniffa, Muzlifah Nature Article Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~140,000 liver and ~74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the impact of tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, NK and ILC precursors in the yolk sac. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for harnessing the therapeutic potential of HSC/MPPs. 2019-10-09 2019-10 /pmc/articles/PMC6861135/ /pubmed/31597962 http://dx.doi.org/10.1038/s41586-019-1652-y Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Popescu, Dorin-Mirel Botting, Rachel A. Stephenson, Emily Green, Kile Webb, Simone Jardine, Laura Calderbank, Emily F. Polanski, Krzysztof Goh, Issac Efremova, Mirjana Acres, Meghan Maunder, Daniel Vegh, Peter Gitton, Yorick Park, Jong-Eun Vento-Tormo, Roser Miao, Zhichao Dixon, David Rowell, Rachel McDonald, David Fletcher, James Poyner, Elizabeth Reynolds, Gary Mather, Michael Moldovan, Corina Mamanova, Lira Greig, Frankie Young, Matthew Meyer, Kerstin B. Lisgo, Steven Bacardit, Jaume Fuller, Andrew Millar, Ben Innes, Barbara Lindsay, Susan Stubbington, Michael J. T. Kowalczyk, Monika S. Li, Bo Ashenbrg, Orr Tabaka, Marcin Dionne, Danielle Tickle, Timothy L. Slyper, Michal Rozenblatt-Rosen, Orit Filby, Andrew Carey, Peter Villani, Alexandra-Chloe Roy, Anindita Regev, Aviv Chedotal, Alain Roberts, Irene Göttgens, Berthold Behjati, Sam Laurenti, Elisa Teichmann, Sarah A. Haniffa, Muzlifah Decoding human fetal liver haematopoiesis |
title | Decoding human fetal liver haematopoiesis |
title_full | Decoding human fetal liver haematopoiesis |
title_fullStr | Decoding human fetal liver haematopoiesis |
title_full_unstemmed | Decoding human fetal liver haematopoiesis |
title_short | Decoding human fetal liver haematopoiesis |
title_sort | decoding human fetal liver haematopoiesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861135/ https://www.ncbi.nlm.nih.gov/pubmed/31597962 http://dx.doi.org/10.1038/s41586-019-1652-y |
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