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A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia.
Baryawno, Ninib; Przybylski, Dariusz; Kowalczyk, Monika S; Kfoury, Youmna; Severe, Nicolas; Gustafsson, Karin; Kokkaliaris, Konstantinos D; Mercier, Francois; Tabaka, Marcin; Hofree, Matan; Dionne, Danielle; Papazian, Ani; Lee, Dongjun; Ashenberg, Orr; Subramanian, Ayshwarya; Vaishnav, Eeshit Dhaval; Rozenblatt-Rosen, Orit; Regev, Aviv; Scadden, David T.
Afiliação
  • Baryawno N; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Childhood Cancer Research Unit, Dep. of Children's and Women
  • Przybylski D; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Kowalczyk MS; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Kfoury Y; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Severe N; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Gustafsson K; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Kokkaliaris KD; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Mercier F; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Tabaka M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Hofree M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Dionne D; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Papazian A; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Lee D; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Convergence Medical Science, Pusan National Un
  • Ashenberg O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Subramanian A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Vaishnav ED; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: aregev@broadinstitute.or
  • Scadden DT; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: david_scadden@harvard.edu.
Cell ; 177(7): 1915-1932.e16, 2019 06 13.
Article em En | MEDLINE | ID: mdl-31130381
ABSTRACT
Stroma 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoblastos / Osteogênese / Células da Medula Óssea / Leucemia Mieloide Aguda / Diferenciação Celular / Microambiente Tumoral / Homeostase Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoblastos / Osteogênese / Células da Medula Óssea / Leucemia Mieloide Aguda / Diferenciação Celular / Microambiente Tumoral / Homeostase Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article