Decoding human fetal liver haematopoiesis

被引：373

作者：

Popescu, Dorin-Mirel ^{[1
]}

Botting, Rachel A. ^{[1
]}

Stephenson, Emily ^{[1
]}

Green, Kile ^{[1
]}

Webb, Simone ^{[1
]}

Jardine, Laura ^{[1
]}

Calderbank, Emily F. ^{[2
,3
]}

Polanski, Krzysztof ^{[4
]}

Goh, Issac ^{[1
]}

Efremova, Mirjana ^{[4
]}

Acres, Meghan ^{[1
]}

Maunder, Daniel ^{[1
]}

Vegh, Peter ^{[1
]}

Gitton, Yorick ^{[5
]}

Park, Jong-Eun ^{[4
]}

Vento-Tormo, Roser ^{[4
]}

Miao, Zhichao ^{[4
,6
]}

Dixon, David ^{[1
]}

Rowell, Rachel ^{[1
]}

McDonald, David ^{[1
]}

Fletcher, James ^{[1
]}

Poyner, Elizabeth ^{[1
,7
,8
]}

Reynolds, Gary ^{[1
]}

Mather, Michael ^{[1
]}

Moldovan, Corina ^{[9
]}

Mamanova, Lira ^{[4
]}

Greig, Frankie ^{[1
]}

Young, Matthew D. ^{[4
]}

Meyer, Kerstin B. ^{[4
]}

Lisgo, Steven ^{[10
]}

Bacardit, Jaume ^{[11
]}

Fuller, Andrew ^{[1
]}

Millar, Ben ^{[1
]}

Innes, Barbara ^{[1
]}

Lindsay, Susan ^{[10
]}

Stubbington, Michael J. T. ^{[4
]}

Kowalczyk, Monika S. ^{[12
]}

Li, Bo ^{[12
,13
]}

Ashenberg, Orr ^{[12
]}

Tabaka, Marcin ^{[12
]}

Dionne, Danielle ^{[12
]}

Tickle, Timothy L. ^{[12
,14
]}

Slyper, Michal ^{[12
]}

Rozenblatt-Rosen, Orit ^{[12
]}

Filby, Andrew ^{[1
]}

Carey, Peter ^{[15
]}

Villani, Alexandra-Chloe ^{[13
,16
]}

Roy, Anindita ^{[17
]}

Regev, Aviv ^{[12
,18
]}

Chedotal, Alain ^{[5
]}

机构：

[1] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[2] Univ Cambridge, Dept Haematol, Cambridge, England

[3] Univ Cambridge, Wellcome & MRC Cambridge Stem Cell Inst, Cambridge, England

[4] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge, England

[5] Sorbonne Univ, INSERM, CNRS, Inst Vis, Paris, France

[6] EMBL, EBI, Wellcome Genome Campus, Cambridge, England

[7] Newcastle Hosp NHS Fdn Trust, Dept Dermatol, Newcastle Upon Tyne, Tyne & Wear, England

[8] Newcastle Hosp NHS Fdn Trust, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England

[9] Newcastle Hosp NHS Fdn Trust, Dept Pathol, Newcastle Upon Tyne, Tyne & Wear, England

[10] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England

[11] Newcastle Univ, Sch Comp, Newcastle Upon Tyne, Tyne & Wear, England

[12] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA

[13] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[14] Broad Inst MIT & Harvard, Data Sci Platform, Cambridge, MA 02142 USA

[15] Newcastle Upon Tyne Hosp NHS Fdn Trust, Royal Victoria Infirm, Haematol Dept, Newcastle Upon Tyne, Tyne & Wear, England

[16] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[17] Univ Oxford, Dept Paediat, Oxford, England

[18] MIT, Dept Biol, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Cambridge, MA USA

[19] Univ Oxford, Mol Haematol Unit, MRC, Oxford, England

[20] Univ Oxford, Dept Paediat, Weatherall Inst Mol Med, Oxford, England

[21] NIHR Oxford Biomed Ctr, BRC Blood Theme, Oxford, England

[22] Univ Cambridge, Dept Paediat, Cambridge, England

[23] Univ Cambridge, Dept Phys, Cavendish Lab, Theory Condensed Matter Grp, Cambridge, England

来源：

NATURE | 2019年 / 574卷 / 7778期

基金：

英国生物技术与生命科学研究理事会;

关键词：

CELL DEVELOPMENT; STEM-CELLS; PROGENITORS; POPULATION; ONTOGENY;

D O I：

10.1038/s41586-019-1652-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：365 / +

页数：27

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