Open AccessBlood and immune development in human fetal bone marrow and Down syndrome
Author(s) -
Laura Jardine,
Simone Webb,
Issac Goh,
Mariana Quiroga Londoño,
Gary Reynolds,
Michael Mather,
Bayanne Olabi,
Emily Stephenson,
Rachel A. Botting,
Dave Horsfall,
Justin Engelbert,
Daniel Maunder,
Nicole Mende,
Caitlin Murnane,
Emma Dann,
Jim McGrath,
Hamish W. King,
Iwo Kuciński,
Rachel Queen,
Christopher D. Carey,
Caroline Shrubsole,
Elizabeth Poyner,
Meghan Acres,
Claire Jones,
Thomas Neß,
Rowen Coulthard,
Natalina E. Elliott,
Sorcha O’Byrne,
Myriam Haltalli,
John S. Lawrence,
Steven Lisgo,
Petra Balogh,
Kerstin B. Meyer,
Elena Prigmore,
Kirsty Ambridge,
Mika Sarkin Jain,
Mirjana Efremova,
Keir Pickard,
Thomas Creasey,
Jaume Bacardit,
Deborah J. Henderson,
Jonathan Coxhead,
Andrew Filby,
Rafiqul Hussain,
David Dixon,
David McDonald,
Dorin-Mirel Popescu,
Monika S. Kowalczyk,
Bo Li,
Orr Ashenberg,
Marcin Tabaka,
Danielle Dionne,
Timothy L. Tickle,
Michal Slyper,
Orit Rozenblatt-Rosen,
Aviv Regev,
Sam Behjati,
Elisa Laurenti,
Nicola K. Wilson,
Anindita Roy,
Berthold Göttgens,
Irene Roberts,
Sarah A. Teichmann,
Muzlifah Haniffa
Publication year - 2021
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-021-03929-x
Subject(s) - haematopoiesis , bone marrow , immune system , biology , myeloid , erythropoiesis , fetus , immunology , cord blood , stromal cell , progenitor cell , stem cell , microbiology and biotechnology , medicine , cancer research , genetics , pregnancy , anemia
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).