title: Signaling Pathways and Gene Regulatory Networks in Cardiomyocyte Differentiation.
abstract: Strategies for harnessing stem cells as a source to treat cell loss in heart disease are the subject of intense research. Human pluripotent stem cells (hPSCs) can be expanded extensively in vitro and therefore can potentially provide sufficient quantities of patient-specific differentiated cardiomyocytes. Although multiple stimuli direct heart development, the differentiation process is driven in large part by signaling activity. The engineering of hPSCs to heart cell progeny has extensively relied on establishing proper combinations of soluble signals, which target genetic programs thereby inducing cardiomyocyte specification. Pertinent differentiation strategies have relied as a template on the development of embryonic heart in multiple model organisms. Here, information on the regulation of cardiomyocyte development from in vivo genetic and embryological studies is critically reviewed. A fresh interpretation is provided of in vivo and in vitro data on signaling pathways and gene regulatory networks (GRNs) underlying cardiopoiesis. The state-of-the-art understanding of signaling pathways and GRNs presented here can inform the design and optimization of methods for the engineering of tissues for heart therapies.
authors: 1 Lonza Walkersville, Inc. , Lonza Group, Walkersville, Maryland.
authors: Abhirath
authors: A
authors: Parikh
authors: 2 Department of Chemical and Biological Engineering, Tufts University , Medford, Massachusetts.
authors: Jincheng
authors: J
authors: Wu
authors: 3 Division of Cardiology, Molecular Cardiology Research Institute , Tufts Medical Center, Tufts School of Medicine, Boston, Massachusetts.
authors: Robert M
authors: RM
authors: Blanton
authors: 2 Department of Chemical and Biological Engineering, Tufts University , Medford, Massachusetts.|4 Tufts Clinical and Translational Science Institute (CTSI) , Boston, Massachusetts.
authors: Emmanuel S
authors: ES
authors: Tzanakakis
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D053263:Gene Regulatory Networks; D006321:Heart / Q000196:embryology; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology; D015398:Signal Transduction / Q000235:genetics*