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In Situ Modification of Tissue Stem and Progenitor Cell Genomes.
Goldstein, Jill M; Tabebordbar, Mohammadsharif; Zhu, Kexian; Wang, Leo D; Messemer, Kathleen A; Peacker, Bryan; Ashrafi Kakhki, Sara; Gonzalez-Celeiro, Meryem; Shwartz, Yulia; Cheng, Jason K W; Xiao, Ru; Barungi, Trisha; Albright, Charles; Hsu, Ya-Chieh; Vandenberghe, Luk H; Wagers, Amy J.
Afiliación
  • Goldstein JM; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
  • Tabebordbar M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Zhu K; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Harvard U
  • Wang LD; Joslin Diabetes Center, Boston, MA 02215, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Messemer KA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
  • Peacker B; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
  • Ashrafi Kakhki S; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
  • Gonzalez-Celeiro M; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
  • Shwartz Y; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Cheng JKW; Editas Medicine, Inc., 11 Hurley Street, Cambridge, MA 02142, USA.
  • Xiao R; Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
  • Barungi T; Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
  • Albright C; Editas Medicine, Inc., 11 Hurley Street, Cambridge, MA 02142, USA.
  • Hsu YC; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Vandenberghe LH; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Boston, MA 02114, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Me
  • Wagers AJ; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Joslin Diabetes Center, Boston, MA 02215, USA. Electron
Cell Rep ; 27(4): 1254-1264.e7, 2019 04 23.
Article en En | MEDLINE | ID: mdl-31018138
In vivo delivery of genome-modifying enzymes holds significant promise for therapeutic applications and functional genetic screening. Delivery to endogenous tissue stem cells, which provide an enduring source of cell replacement during homeostasis and regeneration, is of particular interest. Here, we use a sensitive Cre/lox fluorescent reporter system to test the efficiency of genome modification following in vivo transduction by adeno-associated viruses (AAVs) in tissue stem and progenitor cells. We combine immunophenotypic analyses with in vitro and in vivo assays of stem cell function to reveal effective targeting of skeletal muscle satellite cells, mesenchymal progenitors, hematopoietic stem cells, and dermal cell subsets using multiple AAV serotypes. Genome modification rates achieved through this system reached >60%, and modified cells retained key functional properties. This study establishes a powerful platform to genetically alter tissue progenitors within their physiological niche while preserving their native stem cell properties and regulatory interactions.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Piel / Células Madre Hematopoyéticas / Diferenciación Celular / Genoma / Dependovirus / Células Satélite del Músculo Esquelético Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Piel / Células Madre Hematopoyéticas / Diferenciación Celular / Genoma / Dependovirus / Células Satélite del Músculo Esquelético Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos