In Vivo Cellular Reprogramming: The Next Generation.
Cellular reprogramming technology has created new opportunities in understanding human disease, drug discovery, and regenerative medicine. While a combinatorial code was initially found to reprogram somatic cells to pluripotency, a "second generation" of cellular reprogramming involves lineage-restricted transcription factors and microRNAs that directly reprogram one somatic cell to another. This technology was enabled by gene networks active during development, which induce global shifts in the epigenetic landscape driving cell fate decisions. A major utility of direct reprogramming is the potential of harnessing resident support cells within damaged organs to regenerate lost tissue by converting them into the desired cell type in situ. Here, we review the progress in direct cellular reprogramming, with a focus on the paradigm of in vivo reprogramming for regenerative medicine, while pointing to hurdles that must be overcome to translate this technology into future therapeutics.
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94158, USA; Roddenberry Stem Cell Center at Gladstone, University of California, San Francisco, San Francisco, CA 94158, USA; Departments of Pediatrics and Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: dsrivastava@gladstone.ucsf.edu.
Deepak
D
Srivastava
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
Natalie
N
DeWitt
D065150:Cellular Reprogramming; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D050417:Insulin-Secreting Cells / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology; D009474:Neurons / Q000166:cytology; D044968:Regenerative Medicine / Q000639:trends*; D012106:Research / Q000639:trends; D057170:Translational Research, Biomedical / Q000592:standards / Q000639:trends