Blood and immune development in human fetal bone marrow and Down syndrome

被引：92

作者：

Jardine, Laura ^{[1
,2
]}

Webb, Simone ^{[1
]}

Goh, Issac ^{[1
]}

Londono, Mariana Quiroga ^{[3
]}

Reynolds, Gary ^{[1
]}

Mather, Michael ^{[1
]}

Olabi, Bayanne ^{[1
]}

Stephenson, Emily ^{[1
]}

Botting, Rachel A. ^{[1
]}

Horsfall, Dave ^{[1
]}

Engelbert, Justin ^{[1
]}

Maunder, Daniel ^{[1
]}

Mende, Nicole ^{[3
]}

Murnane, Caitlin ^{[4
]}

Dann, Emma ^{[5
]}

McGrath, Jim ^{[1
]}

King, Hamish ^{[6
]}

Kucinski, Iwo ^{[3
]}

Queen, Rachel ^{[1
]}

Carey, Christopher D. ^{[7
]}

Shrubsole, Caroline ^{[2
]}

Poyner, Elizabeth ^{[1
]}

Acres, Meghan ^{[1
]}

Jones, Claire ^{[8
]}

Ness, Thomas ^{[8
]}

Coulthard, Rowen ^{[8
]}

Elliott, Natalina ^{[4
]}

O'Byrne, Sorcha ^{[4
]}

Haltalli, Myriam L. R. ^{[3
]}

Lawrence, John E. ^{[5
]}

Lisgo, Steven ^{[1
]}

Balogh, Petra ^{[5
]}

Meyer, Kerstin B. ^{[5
]}

Prigmore, Elena ^{[5
]}

Ambridge, Kirsty ^{[5
]}

Jain, Mika Sarkin ^{[5
]}

Efremova, Mirjana ^{[9
]}

Pickard, Keir ^{[2
]}

Creasey, Thomas ^{[2
,10
]}

Bacardit, Jaume ^{[11
]}

Henderson, Deborah ^{[1
]}

Coxhead, Jonathan ^{[1
]}

Filby, Andrew ^{[1
]}

Hussain, Rafiqul ^{[1
]}

Dixon, David ^{[1
]}

McDonald, David ^{[1
]}

Popescu, Dorin-Mirel ^{[1
]}

Kowalczyk, Monika S. ^{[12
]}

Li, Bo ^{[12
]}

Ashenberg, Orr ^{[12
,13
]}

机构：

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

[2] Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Haematol Dept, Newcastle Upon Tyne, Tyne & Wear, England

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

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

[5] Wellcome Sanger Inst, Hinxton, England

[6] Queen Mary Univ London, Ctr Immunobiol, Blizard Inst, London, England

[7] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England

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

[9] Queen Mary Univ London, Barts Canc Inst, London, England

[10] Newcastle Univ, Wolfson Childhood Canc Ctr, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England

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

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

[13] Genentech Inc, San Francisco, CA 94080 USA

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

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

[16] Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England

[17] Univ Oxford, Childrens Hosp, John Radcliffe Hosp, Dept Paediat, Oxford, England

[18] Univ Oxford, MRC WIMM, Oxford, England

[19] Natl Inst Hlth Res NIHR Oxford Biomed Res Ctr, BRC Blood Theme, Oxford, England

[20] Univ Cambridge, Cavendish Lab, Theory Condensed Matter Grp, Cambridge, England

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

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

来源：

NATURE | 2021年 / 598卷 / 7880期

基金：

英国医学研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

HEMATOPOIETIC STEM; CELL;

D O I：

10.1038/s41586-021-03929-x

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：

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception(1,2), yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).

引用

页码：327 / +

页数：35

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