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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
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.
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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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