biostudies-literatureJardine LBarts CharityMedical Research CouncilBlood Cancer UKNational Institute for Health Research (NIHR)Leukaemia UKDBT/Wellcome Trust India AllianceWellcome TrustBiotechnology and Biological Sciences Research CouncilAcademy of Medical Sciences327-331https://www.ebi.ac.uk/biostudies/studies/S-EPMC7612688biostudies-literatureUnknown598(7880)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 iNatureBlood and immune development in human fetal bone marrow and Down syndrome.PMC76126881076302166322020/JGF/002206194107931MR/W014556/1ACF-2017-14-012MC_PC_17230MR/S036113/1MR/N005872/1WT107931/Z/15/ZBB/P002293/1MGU0459WT206194206328MR/S036334/1MR/R006237/1221052MGU0460MR/M008975/1214539/Z/18/Z107630/Z/15/ZWT211276/Z/18/Z215116NIHR-INF-0592211276211276/Z/18/ZSGL015\1021MC_UU_12009/14NIHR-INF-0830216632/Z/19/ZCL-2015-01-002203151/Z/16/ZCL-2016-01-001213555/Z/18/Z206328/Z/17/ZMcDonald DCoulthard RQueen RHaniffa MStephenson EAshenberg OJain MSElliott NHaltalli MLRWilson NKMather MEfremova MAcres MHussain RBalogh PGoh IDixon DDann EReynolds GHorsfall DLisgo SSlyper MQuiroga Londono MAmbridge KRozenblatt-Rosen OJardine LShrubsole CMurnane CNess TKucinski IDionne DBehjati SHenderson DLaurenti EPrigmore EMeyer KBMcGrath JMaunder DJones CWebb SCoxhead JLi BCreasey TFilby ACarey CDEngelbert JPopescu DMGottgens BKowalczyk MSKing HRoy ATabaka MBacardit JTickle TLPoyner EOlabi BMende NPickard KRegev AO'Byrne SBotting RALawrence JERoberts ITeichmann SAfalseBlood and immune development in human fetal bone marrow and Down syndrome.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 i2021-01-01T00:00:00Z2021 Oct2025-04-21T21:30:59.765Z2025-04-05T18:21:50.176ZS-EPMC76126883458869310.1038/s41586-021-03929-x