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The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression.
Mehta, Arnav; Zhao, Jimmy L; Sinha, Nikita; Marinov, Georgi K; Mann, Mati; Kowalczyk, Monika S; Galimidi, Rachel P; Du, Xiaomi; Erikci, Erdem; Regev, Aviv; Chowdhury, Kamal; Baltimore, David.
Afiliación
  • Mehta A; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zhao JL; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sinha N; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Marinov GK; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Mann M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Kowalczyk MS; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Galimidi RP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Du X; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Erikci E; Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Gottingen 37077, Germany.
  • Regev A; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
  • Chowdhury K; Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Gottingen 37077, Germany.
  • Baltimore D; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: baltimo@caltech.edu.
Immunity ; 42(6): 1021-32, 2015 Jun 16.
Article en En | MEDLINE | ID: mdl-26084022
ABSTRACT
MicroRNAs are critical post-transcriptional regulators of hematopoietic cell-fate decisions, though little remains known about their role in aging hematopoietic stem cells (HSCs). We found that the microRNA-212/132 cluster (Mirc19) is enriched in HSCs and is upregulated during aging. Both overexpression and deletion of microRNAs in this cluster leads to inappropriate hematopoiesis with age. Enforced expression of miR-132 in the bone marrow of mice led to rapid HSC cycling and depletion. A genetic deletion of Mirc19 in mice resulted in HSCs that had altered cycling, function, and survival in response to growth factor starvation. We found that miR-132 exerted its effect on aging HSCs by targeting the transcription factor FOXO3, a known aging associated gene. Our data demonstrate that Mirc19 plays a role in maintaining balanced hematopoietic output by buffering FOXO3 expression. We have thus identified it as a potential target that might play a role in age-related hematopoietic defects.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células de la Médula Ósea / Células Madre Hematopoyéticas / MicroARNs / Factores de Transcripción Forkhead / Hematopoyesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células de la Médula Ósea / Células Madre Hematopoyéticas / MicroARNs / Factores de Transcripción Forkhead / Hematopoyesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos