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dc.contributor.authorBaryawno, Ninib
dc.contributor.authorPrzybylski, Dariusz
dc.contributor.authorKowalczyk, Monika S.
dc.contributor.authorKfoury, Youmna
dc.contributor.authorSevere, Nicolas
dc.contributor.authorGustafsson, Karin
dc.contributor.authorKokkaliaris, Konstantinos D.
dc.contributor.authorMercier, Francois
dc.contributor.authorTabaka, Marcin
dc.contributor.authorHofree, Matan
dc.contributor.authorDionne, Danielle
dc.contributor.authorPapazian, Ani
dc.contributor.authorLee, Dongjun
dc.contributor.authorAshenberg, Orr
dc.contributor.authorSubramanian, Ayshwarya
dc.contributor.authorVaishnav, Eeshit Dhaval
dc.contributor.authorRozenblatt-Rosen, Orit
dc.contributor.authorRegev, Aviv
dc.contributor.authorScadden, David T.
dc.date.accessioned2020-07-09T14:02:07Z
dc.date.available2020-07-09T14:02:07Z
dc.date.issued2019-06
dc.date.submitted2018-12
dc.identifier.issn0092-8674
dc.identifier.urihttps://hdl.handle.net/1721.1/126112
dc.description.abstractStroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis, and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA sequencing (scRNA-seq) to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. We identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes spanning new fibroblastic and osteoblastic subpopulations including distinct osteoblast differentiation trajectories. Emerging acute myeloid leukemia impaired mesenchymal osteogenic differentiation and reduced regulatory molecules necessary for normal hematopoiesis. These data suggest that tissue stroma responds to malignant cells by disadvantaging normal parenchymal cells. Our taxonomy of the stromal compartment provides a comprehensive bone marrow cell census and experimental support for cancer cell crosstalk with specific stromal elements to impair normal tissue function and thereby enable emergent cancer.en_US
dc.description.sponsorshipNational Institutes of Health (Grant DK107784)en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2019.04.040en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleA Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemiaen_US
dc.typeArticleen_US
dc.identifier.citationBaryawno, Ninib et al. "A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia." Cell 177, 7 (June 2019): P1915-1932.e16 © 2019 Elsevieren_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalCellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-06-19T17:58:30Z
dspace.date.submission2020-06-19T17:58:33Z
mit.journal.volume177en_US
mit.journal.issue7en_US
mit.licensePUBLISHER_CC


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