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Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis.
Khajuria, Rajiv K; Munschauer, Mathias; Ulirsch, Jacob C; Fiorini, Claudia; Ludwig, Leif S; McFarland, Sean K; Abdulhay, Nour J; Specht, Harrison; Keshishian, Hasmik; Mani, D R; Jovanovic, Marko; Ellis, Steven R; Fulco, Charles P; Engreitz, Jesse M; Schütz, Sabina; Lian, John; Gripp, Karen W; Weinberg, Olga K; Pinkus, Geraldine S; Gehrke, Lee; Regev, Aviv; Lander, Eric S; Gazda, Hanna T; Lee, Winston Y; Panse, Vikram G; Carr, Steven A; Sankaran, Vijay G.
Afiliação
  • Khajuria RK; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Berlin-Brandenburg School for Regenerative Therapies, Charité-U
  • Munschauer M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ulirsch JC; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Fiorini C; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ludwig LS; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • McFarland SK; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Abdulhay NJ; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Specht H; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Keshishian H; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Mani DR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jovanovic M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ellis SR; Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202, USA.
  • Fulco CP; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Engreitz JM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Schütz S; Institute of Medical Microbiology, Department of Medicine, University of Zurich, 8006 Zurich, Switzerland.
  • Lian J; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA.
  • Gripp KW; Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, DE 19803, USA.
  • Weinberg OK; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Pinkus GS; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Gehrke L; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA.
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lander ES; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gazda HT; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Lee WY; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Panse VG; Institute of Medical Microbiology, Department of Medicine, University of Zurich, 8006 Zurich, Switzerland.
  • Carr SA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sankaran VG; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: sankaran@broadinstitute.org.
Cell ; 173(1): 90-103.e19, 2018 03 22.
Article em En | MEDLINE | ID: mdl-29551269
ABSTRACT
Blood cell formation is classically thought to occur through a hierarchical differentiation process, although recent studies have shown that lineage commitment may occur earlier in hematopoietic stem and progenitor cells (HSPCs). The relevance to human blood diseases and the underlying regulation of these refined models remain poorly understood. By studying a genetic blood disorder, Diamond-Blackfan anemia (DBA), where the majority of mutations affect ribosomal proteins and the erythroid lineage is selectively perturbed, we are able to gain mechanistic insight into how lineage commitment is programmed normally and disrupted in disease. We show that in DBA, the pool of available ribosomes is limited, while ribosome composition remains constant. Surprisingly, this global reduction in ribosome levels more profoundly alters translation of a select subset of transcripts. We show how the reduced translation of select transcripts in HSPCs can impair erythroid lineage commitment, illuminating a regulatory role for ribosome levels in cellular differentiation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article