1. Blood and immune development in human fetal bone marrow and Down syndrome.
- Author
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Jardine L, Webb S, Goh I, Quiroga Londoño M, Reynolds G, Mather M, Olabi B, Stephenson E, Botting RA, Horsfall D, Engelbert J, Maunder D, Mende N, Murnane C, Dann E, McGrath J, King H, Kucinski I, Queen R, Carey CD, Shrubsole C, Poyner E, Acres M, Jones C, Ness T, Coulthard R, Elliott N, O'Byrne S, Haltalli MLR, Lawrence JE, Lisgo S, Balogh P, Meyer KB, Prigmore E, Ambridge K, Jain MS, Efremova M, Pickard K, Creasey T, Bacardit J, Henderson D, Coxhead J, Filby A, Hussain R, Dixon D, McDonald D, Popescu DM, Kowalczyk MS, Li B, Ashenberg O, Tabaka M, Dionne D, Tickle TL, Slyper M, Rozenblatt-Rosen O, Regev A, Behjati S, Laurenti E, Wilson NK, Roy A, Göttgens B, Roberts I, Teichmann SA, and Haniffa M
- Subjects
- B-Lymphocytes cytology, Dendritic Cells cytology, Down Syndrome metabolism, Down Syndrome pathology, Endothelial Cells pathology, Eosinophils cytology, Erythroid Cells cytology, Granulocytes cytology, Humans, Immunity, Myeloid Cells cytology, Stromal Cells cytology, Bone Marrow, Bone Marrow Cells cytology, Down Syndrome blood, Down Syndrome immunology, Fetus cytology, Hematopoiesis, Immune System cytology
- Abstract
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)., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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