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dc.contributor.authorJardine, Laura
dc.contributor.authorWebb, Simone
dc.contributor.authorGoh, Issac
dc.contributor.authorQuiroga Londoño, Mariana
dc.contributor.authorReynolds, Gary
dc.contributor.authorMather, Michael
dc.contributor.authorOlabi, Bayanne
dc.contributor.authorStephenson, Emily
dc.contributor.authorBotting, Rachel A
dc.contributor.authorHorsfall, Dave
dc.contributor.authorEngelbert, Justin
dc.contributor.authorMaunder, Daniel
dc.contributor.authorMende, Nicole
dc.contributor.authorMurnane, Caitlin
dc.contributor.authorDann, Emma
dc.contributor.authorMcGrath, Jim
dc.contributor.authorKing, Hamish
dc.contributor.authorKucinski, Iwo
dc.contributor.authorQueen, Rachel
dc.contributor.authorCarey, Christopher D
dc.contributor.authorShrubsole, Caroline
dc.contributor.authorPoyner, Elizabeth
dc.contributor.authorAcres, Meghan
dc.contributor.authorJones, Claire
dc.contributor.authorNess, Thomas
dc.contributor.authorCoulthard, Rowen
dc.contributor.authorElliott, Natalina
dc.contributor.authorO'Byrne, Sorcha
dc.contributor.authorHaltalli, Myriam
dc.contributor.authorLawrence, John E
dc.contributor.authorLisgo, Steven
dc.contributor.authorBalogh, Petra
dc.contributor.authorMeyer, Kerstin B
dc.contributor.authorPrigmore, Elena
dc.contributor.authorAmbridge, Kirsty
dc.contributor.authorJain, Mika Sarkin
dc.contributor.authorEfremova, Mirjana
dc.contributor.authorPickard, Keir
dc.contributor.authorCreasey, Thomas
dc.contributor.authorBacardit, Jaume
dc.contributor.authorHenderson, Deborah
dc.contributor.authorCoxhead, Jonathan
dc.contributor.authorFilby, Andrew
dc.contributor.authorHussain, Rafiqul
dc.contributor.authorDixon, David
dc.contributor.authorMcDonald, David
dc.contributor.authorPopescu, Dorin-Mirel
dc.contributor.authorKowalczyk, Monika S
dc.contributor.authorLi, Bo
dc.contributor.authorAshenberg, Orr
dc.contributor.authorTabaka, Marcin
dc.contributor.authorDionne, Danielle
dc.contributor.authorTickle, Timothy L
dc.contributor.authorSlyper, Michal
dc.contributor.authorRozenblatt-Rosen, Orit
dc.contributor.authorRegev, Aviv
dc.contributor.authorBehjati, Sam
dc.contributor.authorLaurenti, Elisa
dc.contributor.authorWilson, Nicola
dc.contributor.authorRoy, Anindita
dc.contributor.authorGottgens, Berthold
dc.contributor.authorRoberts, Irene
dc.contributor.authorTeichmann, Sarah
dc.contributor.authorHaniffa, Muzlifah
dc.date.accessioned2021-10-07T23:30:48Z
dc.date.available2021-10-07T23:30:48Z
dc.date.issued2021-10
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329122
dc.description.abstractHaematopoiesis 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).
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.titleBlood and immune development in human fetal bone marrow and Down syndrome.
dc.typeArticle
prism.endingPage331
prism.issueIdentifier7880
prism.publicationDate2021
prism.publicationNameNature
prism.startingPage327
prism.volume598
dc.identifier.doi10.17863/CAM.76568
dcterms.dateAccepted2021-08-18
rioxxterms.versionofrecord10.1038/s41586-021-03929-x
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-10
dc.contributor.orcidWebb, Simone [0000-0003-3058-8952]
dc.contributor.orcidGoh, Issac [0000-0002-6397-3518]
dc.contributor.orcidQuiroga Londoño, Mariana [0000-0003-2352-0773]
dc.contributor.orcidMather, Michael [0000-0001-7972-7111]
dc.contributor.orcidBotting, Rachel A [0000-0001-9595-4605]
dc.contributor.orcidHorsfall, Dave [0000-0002-8086-812X]
dc.contributor.orcidMende, Nicole [0000-0002-5078-2333]
dc.contributor.orcidDann, Emma [0000-0002-7400-7438]
dc.contributor.orcidKing, Hamish [0000-0001-5972-8926]
dc.contributor.orcidKucinski, Iwo [0000-0002-9385-0359]
dc.contributor.orcidHaltalli, Myriam [0000-0002-0886-4466]
dc.contributor.orcidMeyer, Kerstin B [0000-0001-5906-1498]
dc.contributor.orcidEfremova, Mirjana [0000-0002-8107-9974]
dc.contributor.orcidCreasey, Thomas [0000-0001-8536-5428]
dc.contributor.orcidBacardit, Jaume [0000-0002-2692-7205]
dc.contributor.orcidCoxhead, Jonathan [0000-0002-6128-9560]
dc.contributor.orcidTickle, Timothy L [0000-0002-6592-6272]
dc.contributor.orcidRozenblatt-Rosen, Orit [0000-0001-6313-3570]
dc.contributor.orcidRegev, Aviv [0000-0003-3293-3158]
dc.contributor.orcidBehjati, Sam [0000-0002-6600-7665]
dc.contributor.orcidLaurenti, Elisa [0000-0002-9917-9092]
dc.contributor.orcidWilson, Nicola [0000-0003-0865-7333]
dc.contributor.orcidRoy, Anindita [0000-0001-8607-5748]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidTeichmann, Sarah [0000-0002-6294-6366]
dc.contributor.orcidHaniffa, Muzlifah [0000-0002-3927-2084]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/M008975/1)
pubs.funder-project-idWellcome Trust (107630/Z/15/Z)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P002293/1)
pubs.funder-project-idWellcome Trust (206328/Z/17/Z)
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idMedical Research Council (MR/S036113/1)
cam.issuedOnline2021-09-29
cam.orpheus.successMon Oct 11 07:30:22 BST 2021 - Embargo updated
rioxxterms.freetoread.startdate2022-03-29


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