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Decoding human fetal liver haematopoiesis

by Innes, Barbara , Tabaka, Marcin , Reynolds, Gary , Slyper, Michal , Young, Matthew D. , McDonald, David , Lisgo, Steven , Chédotal, Alain , Botting, Rachel A. , Dionne, Danielle , Mamanova, Lira , Teichmann, Sarah A. , Roberts, Irene , Fuller, Andrew , Park, Jong-Eun , Behjati, Sam , Goh, Issac , Vegh, Peter , Carey, Peter , Miao, Zhichao , Lindsay, Susan , Mather, Michael , Gitton, Yorick , Moldovan, Corina , Regev, Aviv , Bacardit, Jaume , Millar, Ben , Polanski, Krzysztof , Tickle, Timothy L. , Acres, Meghan , Maunder, Daniel , Stubbington, Michael J. T. , Meyer, Kerstin B. , Filby, Andrew , Rowell, Rachel , Vento-Tormo, Roser , Fletcher, James , Poyner, Elizabeth , Roy, Anindita , Haniffa, Muzlifah , Popescu, Dorin-Mirel , Villani, Alexandra-Chloé , Ashenberg, Orr , Calderbank, Emily F. , Göttgens, Berthold , Green, Kile , Webb, Simone , Rozenblatt-Rosen, Orit , Laurenti, Elisa , Efremova, Mirjana , Li, Bo , Kowalczyk, Monika S. , Greig, Frankie , Stephenson, Emily , Jardine, Laura , Dixon, David

in 13/106 / 13/31 / 14 / 14/63 / 38 / 38/91 / 631/114/2415 / 631/136/232/1997 / 631/208/514/1949 / 631/250/232/1997 / Blood / Blood Cells - cytology / Bone marrow / Cell differentiation / Cell self-renewal / Cellular Microenvironment / DNA testing / Erythropoiesis / Female / Fetal tissues / Fetus - cytology / Fetus - metabolism / Fetuses / Flow Cytometry / Gene expression / Gene Expression Profiling / Genes / Genetic aspects / Genomics / Gestation / Hematopoiesis / Hematopoietic stem cells / Humanities and Social Sciences / Humans / Identification and classification / Immune system / Life Sciences / Liver / Liver - cytology / Liver - embryology / Liver - metabolism / Liver cells / Lymphoid Tissue - cytology / Mast cells / Methods / multidisciplinary / Natural killer cells / Science / Science (multidisciplinary) / Single-Cell Analysis / Stem cells / Stem Cells - metabolism / Yolk / Yolk sac

2019

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Decoding human fetal liver haematopoiesis

2019

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2019

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Journal Article

Decoding human fetal liver haematopoiesis

Innes, Barbara,

Tabaka, Marcin,

Reynolds, Gary,

Slyper, Michal,

Young, Matthew D.,

McDonald, David,

Lisgo, Steven,

Chédotal, Alain,

Botting, Rachel A.,

Dionne, Danielle,

Mamanova, Lira,

Teichmann, Sarah A.,

Roberts, Irene,

Fuller, Andrew,

Park, Jong-Eun,

Behjati, Sam,

Goh, Issac,

Vegh, Peter,

Carey, Peter,

Miao, Zhichao,

Lindsay, Susan,

Mather, Michael,

Gitton, Yorick,

Moldovan, Corina,

Regev, Aviv,

Bacardit, Jaume,

Millar, Ben,

Polanski, Krzysztof,

Tickle, Timothy L.,

Acres, Meghan,

Maunder, Daniel,

Stubbington, Michael J. T.,

Meyer, Kerstin B.,

Filby, Andrew,

Rowell, Rachel,

Vento-Tormo, Roser,

Fletcher, James,

Poyner, Elizabeth,

Roy, Anindita,

Haniffa, Muzlifah,

Popescu, Dorin-Mirel,

Villani, Alexandra-Chloé,

Ashenberg, Orr,

Calderbank, Emily F.,

Göttgens, Berthold,

Green, Kile,

Webb, Simone,

Rozenblatt-Rosen, Orit,

Laurenti, Elisa,

Efremova, Mirjana,

Li, Bo,

Kowalczyk, Monika S.,

Greig, Frankie,

Stephenson, Emily,

Jardine, Laura,

Dixon, David

2019

Overview

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 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 influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, 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 reference for harnessing the therapeutic potential of HSC/MPPs. Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

13/106

/ 13/31

/ 14

/ 14/63

/ 38

/ 38/91

/ 631/114/2415