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

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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Oh Y,Cho GS,Li Z,Hong I,Zhu R,Kim MJ,Kim YJ,Tampakakis E,Tung L,Huganir R,Dong X,Kwon C,Lee G

doi

10.1016/j.stem.2016.05.002

subject

Has Abstract

pub_date

2016-07-07 00:00:00

pages

95-106

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(16)30086-8

journal_volume

19

pub_type

杂志文章

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