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Decoding the development of the blood and immune systems during human fetal liver haematopoiesis

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

in Blood / Cell self-renewal / Developmental Biology / Erythropoiesis / Fetuses / Gene expression / Gestation / Hematopoietic stem cells / Liver / Prenatal development / Skin / Stem cells

2019

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Decoding the development of the blood and immune systems during human fetal liver haematopoiesis

in Blood / Cell self-renewal / Developmental Biology / Erythropoiesis / Fetuses / Gene expression / Gestation / Hematopoietic stem cells / Liver / Prenatal development / Skin / Stem cells

2019

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Decoding the development of the blood and immune systems during human fetal liver haematopoiesis

in Blood / Cell self-renewal / Developmental Biology / Erythropoiesis / Fetuses / Gene expression / Gestation / Hematopoietic stem cells / Liver / Prenatal development / Skin / Stem cells

2019

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Paper

Decoding the development of the blood and immune systems during human fetal liver haematopoiesis

Innes, Barbara,

Tabaka, Marcin D,

Reynolds, Gary,

Slyper, Michal,

Lisgo, Steven,

Park, Jongeun,

Dionne, Danielle,

Young, Matthew D,

Roberts, Irene,

Calderbank, Emily F,

Fuller, Andrew,

Behjati, Sam,

Goh, Issac,

Vegh, Peter,

Miao, Zhichao,

Li, Bo D,

Chedotal, Alain,

Lindsay, Susan,

Michael Jt Stubbington,

Mather, Michael,

Gitton, Yorick,

Moldovan, Corina,

Botting, Rachel A,

Bacardit, Jaume,

Millar, Ben,

Polanski, Krzysztof,

Acres, Meghan,

Maunder, Daniel,

Filby, Andrew,

Rowell, Rachel,

Mcdonald, David,

Gottgens, Berthold D,

Vento-Tormo, Roser,

Fletcher, James,

Regev, Aviv D,

Teichmann, Sarah D,

Orr Ashenbrg,

Poyner, Elizabeth,

Roy, Anindita,

Haniffa, Muzlifah,

Popescu, Dorin-Mirel,

Villani, Alexandra-Chloe,

Meyer, Kerstin,

Green, Kile,

Rozenblatt-Rosen, Orit,

Laurenti, Elisa,

Efremova, Mirjana,

Kowalczyk, Monika D,

Lira Mamanova,

Greig, Frankie,

Tickle, Timothy L,

Stephenson, Emily,

Jardine, Laura,

Dixon, David

2019

Overview

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs), yet remains poorly defined in humans. Using single cell transcriptome profiling of ~133,000 fetal liver and ~65,000 fetal skin and kidney cells, we identify the repertoire of blood and immune cells in first and early second trimesters of development. From this data, we infer differentiation trajectories from HSC/MPPs, and evaluate the impact of tissue microenvironment on blood and immune cell development. We predict coupling of mast cell differentiation with erythro-megakaryopoiesis and identify physiological erythropoiesis in fetal skin. 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 understanding and harnessing the therapeutic potential of HSC/MPPs. Footnotes * http://developmentcellatlas.ncl.ac.uk/datasets/liver_10x

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Publisher

Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory

Subject

Blood

/ Cell self-renewal

/ Developmental Biology

/ Erythropoiesis

/ Fetuses

/ Gene expression

/ Gestation