Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons

Yohan Oh, Gun Sik Cho, Min Jeong Kim, Yong Jun Kim, Chulan Kwon, Gabsang Lee

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)95-106
Number of pages12
JournalCell stem cell
Volume19
Issue number1
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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