한빛사 논문
Abstract
Yohan Oh1, 2, 3, Gun-Sik Cho1, 4, Zhe Li5, Ingie Hong5, Renjun Zhu6, Min-Jeong Kim1, 2, 9, Yong Jun Kim1, 2, 10, Emmanouil Tampakakis4, Leslie Tung6, Richard Huganir5, Xinzhong Dong5, 7, 8, Chulan Kwon1, 4,*, Gabsang Lee1, 2, 3, 5, *,
1 Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA
4 Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5 The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
6 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
7 Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
8 The Howard Hughes Medical Institute, Baltimore, MD 21205, USA
9 Present address: Stem Cell & Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea
10 Present address: Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130-701, Korea
*Corresponding authors
Summary
Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but it has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show that they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B::eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX2B::eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기