Citation

Goldstein JM, Tabebordbar M, Zhu K, Wang LD, Messemer KA, Peacker B, Ashrafi Kakhki S, Gonzalez-Celeiro M, Shwartz Y, Cheng JKW, Xiao R, Barungi T, Albright C, Hsu YC, Vandenberghe LH, Wagers AJ. 2019. In Situ Modification of Tissue Stem and Progenitor Cell Genomes. Cell reports. 27(4):1254-1264.e7. Pubmed: 31018138

Abstract

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.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Related Faculty

Photo of Amy Wagers

Amy Wagers seeks to change the way we repair our tissues after an injury. Her research focuses on defining the factors and mechanisms that regulate the migration, expansion, and regenerative potential of adult blood-forming and muscle-forming stem cells.

Photo of Ya-Chieh Hsu

Ya-Chieh Hsu studies the principles and molecular nature of cell-cell interactions governing development, regeneration, and injury repair in the skin.

Photo of Jill Marie Goldstein

Jill’s research focuses on identifying therapeutically relevant ways to restore healthy function to tissues in the contexts of aging and disease.

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