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

Autor: Nicola K. Wilson, Michal Slyper, David Dixon, Gary Reynolds, Emily Stephenson, Berthold Göttgens, Irene Roberts, Petra Balogh, Anindita Roy, Bo Li, Monika S. Kowalczyk, Aviv Regev, Nicole Mende, Hamish W King, Iwo Kucinski, Laura Jardine, Mirjana Efremova, Meghan Acres, Orr Ashenberg, Caroline Shrubsole, Thomas Creasey, Dave Horsfall, Mika Sarkin Jain, Simone Webb, Elizabeth Poyner, Steven Lisgo, Rachel Queen, Kerstin B. Meyer, Kirsty Ambridge, John E. Lawrence, Natalina Elliott, Elena Prigmore, Jaume Bacardit, Rachel A. Botting, Danielle Dionne, Muzlifah Haniffa, Justin Engelbert, Marcin Tabaka, Rafiqul Hussain, Myriam L. R. Haltalli, Christopher D. Carey, Thomas Ness, Bayanne Olabi, Deborah J. Henderson, Daniel Maunder, Elisa Laurenti, Keir Pickard, Orit Rozenblatt-Rosen, Rowen Coulthard, Jim McGrath, Sam Behjati, Issac Goh, David McDonald, Sorcha O’Byrne, Timothy L. Tickle, Emma Dann, Claire G. Jones, Sarah A. Teichmann, Caitlin Murnane, Dorin-Mirel Popescu, Jonathan Coxhead, Mariana Quiroga Londoño, Michael W. Mather, Andrew Filby
Přispěvatelé: Webb, Simone [0000-0003-3058-8952], Goh, Issac [0000-0002-6397-3518], Quiroga Londoño, Mariana [0000-0003-2352-0773], Mather, Michael [0000-0001-7972-7111], Botting, Rachel A [0000-0001-9595-4605], Horsfall, Dave [0000-0002-8086-812X], Mende, Nicole [0000-0002-5078-2333], Dann, Emma [0000-0002-7400-7438], King, Hamish [0000-0001-5972-8926], Kucinski, Iwo [0000-0002-9385-0359], Haltalli, Myriam LR [0000-0002-0886-4466], Meyer, Kerstin B [0000-0001-5906-1498], Efremova, Mirjana [0000-0002-8107-9974], Creasey, Thomas [0000-0001-8536-5428], Bacardit, Jaume [0000-0002-2692-7205], Coxhead, Jonathan [0000-0002-6128-9560], Tickle, Timothy L [0000-0002-6592-6272], Rozenblatt-Rosen, Orit [0000-0001-6313-3570], Regev, Aviv [0000-0003-3293-3158], Behjati, Sam [0000-0002-6600-7665], Laurenti, Elisa [0000-0002-9917-9092], Wilson, Nicola K [0000-0003-0865-7333], Roy, Anindita [0000-0001-8607-5748], Göttgens, Berthold [0000-0001-6302-5705], Teichmann, Sarah A [0000-0002-6294-6366], Haniffa, Muzlifah [0000-0002-3927-2084], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nature
DOI: 10.1038/s41586-021-03929-x
Popis: 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 conception1,2, 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). A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.
Databáze: OpenAIRE
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