Project 3. Cardiac Differentiation from Human Embryonic Stem Cells (Charles E. Murry, Project Leader) The long term goals of this work are to understand pathways controlling differentiation of cardiomyocytes from human embryonic stem cells (hESCs). These pluripotent cells offer a system for basic research in human development and cell biology, as well as potential applications for tissue repair and regeneration. Traditional ESC differentiation systems, such as embryoid bodies, are heterogeneous and yield cardiomyocytes at low efficiency, typically <1%. This lack of purity and low yield has significantly impeded research. In collaboration with colleagues at Geron, we recently developed a system for directed differentiation of hESCs, using Activin A and BMP4, which yields -50% cardiomyocytes before purification and >95% myocytes after purification. Furthermore, in collaboration with Dr. Moon's laboratory (Project 2), we have shown a potent role for Wnt/b-catenin signaling in control of cardiogenesis in mouse ESCs. The ability to efficiently control ESC differentiation makes possible systematic studies into the mechanism of human cardiac differentiation and could yield populations of cells, such as pre-cardiac mesodermal progenitors, that have remained elusive due to technical limitations. The current proposal therefore focuses on optimizing these regimens and understanding key molecular and cellular steps in cardiac differentiation from hESCs.
Hofsteen, Peter; Robitaille, Aaron Mark; Strash, Nicholas et al. (2018) ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem Cells. iScience 2:88-100 |
Moody, James D; Levy, Shiri; Mathieu, Julie et al. (2017) First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor. Proc Natl Acad Sci U S A 114:10125-10130 |
Mathieu, Julie; Ruohola-Baker, Hannele (2017) Metabolic remodeling during the loss and acquisition of pluripotency. Development 144:541-551 |
Rabinowitz, Jeremy S; Robitaille, Aaron M; Wang, Yuliang et al. (2017) Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish. Proc Natl Acad Sci U S A 114:E717-E726 |
Eschenhagen, Thomas; Bolli, Roberto; Braun, Thomas et al. (2017) Cardiomyocyte Regeneration: A Consensus Statement. Circulation 136:680-686 |
Ware, Carol B (2017) Concise Review: Lessons from Naïve Human Pluripotent Cells. Stem Cells 35:35-41 |
Palpant, Nathan J; Wang, Yuliang; Hadland, Brandon et al. (2017) Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis. Cell Rep 20:1597-1608 |
Hoshino, Akina; Ratnapriya, Rinki; Brooks, Matthew J et al. (2017) Molecular Anatomy of the Developing Human Retina. Dev Cell 43:763-779.e4 |
Kim, Yong Kyun; Refaeli, Ido; Brooks, Craig R et al. (2017) Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development. Stem Cells 35:2366-2378 |
Artoni, Filippo; Kreipke, Rebecca E; Palmeira, Ondina et al. (2017) Loss of foxo rescues stem cell aging in Drosophila germ line. Elife 6: |
Showing the most recent 10 out of 114 publications