title: Reprogramming fibroblasts toward cardiomyocytes, neural stem cells and hepatocytes by cell activation and signaling-directed lineage conversion.
abstract: Induction of tissue-specific cell types via a conventional transdifferentiation strategy typically uses overexpression of the corresponding lineage-specific transcription factors. Alternatively, somatic cells can be temporarily activated via a common set of reprogramming factors into a transition state, which can then be directed into various cell types via soluble lineage-specific signals, without establishing a pluripotent state. Here, we provide protocols for the generation of cardiomyocytes, neural stem cells and hepatocytes from fibroblasts with such a cell activation (CA) and signaling-directed (SD; CASD) strategy. In these protocols, beating cardiomyocytes can be induced from mouse fibroblasts in 2-5 weeks; expandable neural stem cells and definitive endoderm progenitors can be obtained from human fibroblasts as early as 2.5 weeks; and human definitive endoderm progenitors can be differentiated into functional hepatocytes in 2 weeks. Through further developments, the CASD strategy can serve as a unique avenue for generating diverse functional cell types for biomedical research and therapeutic applications.
authors.affiliation: 1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Roddenberry Center for Stem Cell Biology and Medicine at the Gladstone Institutes, San Francisco, California, USA.
authors.forename: Saiyong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: 1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Roddenberry Center for Stem Cell Biology and Medicine at the Gladstone Institutes, San Francisco, California, USA.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1] Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. [2] Roddenberry Center for Stem Cell Biology and Medicine at the Gladstone Institutes, San Francisco, California, USA. [3] Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D019070:Cell Lineage; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction