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

Yohan Oh, Gun Sik Cho, Zhe Li, Ingie Hong, Chulan Kwon, Gabsang Lee, Yong Jun Kim, Emmanouil Tampakakis, Leslie Tung, Richard Huganir, Xinzhong Dong, Chulan Kwon, Gabsang Lee

Research output: Contribution to journalArticle

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. Oh et al. differentiate human pluripotent stem cells into functional sympathetic neurons that can functionally and physically couple with ventricular cardiomyocytes. This coupling controls cardiomyocyte beating and promotes neuronal maturation, providing a platform for studying neuronal regulation of cardiac behavior and modeling complex intercellular physiology.

Original languageEnglish (US)
JournalCell Stem Cell
DOIs
StateAccepted/In press - Jul 31 2015

Fingerprint

Pluripotent Stem Cells
Myocardium
Neurons
Cardiac Myocytes
Optogenetics
Human Development
Cell Communication
Norepinephrine
Cell Line

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons. / Oh, Yohan; Cho, Gun Sik; Li, Zhe; Hong, Ingie; Kwon, Chulan; Lee, Gabsang; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang.

In: Cell Stem Cell, 31.07.2015.

Research output: Contribution to journalArticle

Oh, Y, Cho, GS, Li, Z, Hong, I, Kwon, C, Lee, G, Kim, YJ, Tampakakis, E, Tung, L, Huganir, R, Dong, X, Kwon, C & Lee, G 2015, 'Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons', Cell Stem Cell. https://doi.org/10.1016/j.stem.2016.05.002
Oh, Yohan ; Cho, Gun Sik ; Li, Zhe ; Hong, Ingie ; Kwon, Chulan ; Lee, Gabsang ; Kim, Yong Jun ; Tampakakis, Emmanouil ; Tung, Leslie ; Huganir, Richard ; Dong, Xinzhong ; Kwon, Chulan ; Lee, Gabsang. / Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons. In: Cell Stem Cell. 2015.
@article{22e0c97a67b54cda8e64e964694dd82b,
title = "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. Oh et al. differentiate human pluripotent stem cells into functional sympathetic neurons that can functionally and physically couple with ventricular cardiomyocytes. This coupling controls cardiomyocyte beating and promotes neuronal maturation, providing a platform for studying neuronal regulation of cardiac behavior and modeling complex intercellular physiology.",
author = "Yohan Oh and Cho, {Gun Sik} and Zhe Li and Ingie Hong and Chulan Kwon and Gabsang Lee and Kim, {Yong Jun} and Emmanouil Tampakakis and Leslie Tung and Richard Huganir and Xinzhong Dong and Chulan Kwon and Gabsang Lee",
year = "2015",
month = "7",
day = "31",
doi = "10.1016/j.stem.2016.05.002",
language = "English (US)",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",

}

TY - JOUR

T1 - Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons

AU - Oh, Yohan

AU - Cho, Gun Sik

AU - Li, Zhe

AU - Hong, Ingie

AU - Kwon, Chulan

AU - Lee, Gabsang

AU - Kim, Yong Jun

AU - Tampakakis, Emmanouil

AU - Tung, Leslie

AU - Huganir, Richard

AU - Dong, Xinzhong

AU - Kwon, Chulan

AU - Lee, Gabsang

PY - 2015/7/31

Y1 - 2015/7/31

N2 - 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. Oh et al. differentiate human pluripotent stem cells into functional sympathetic neurons that can functionally and physically couple with ventricular cardiomyocytes. This coupling controls cardiomyocyte beating and promotes neuronal maturation, providing a platform for studying neuronal regulation of cardiac behavior and modeling complex intercellular physiology.

AB - 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. Oh et al. differentiate human pluripotent stem cells into functional sympathetic neurons that can functionally and physically couple with ventricular cardiomyocytes. This coupling controls cardiomyocyte beating and promotes neuronal maturation, providing a platform for studying neuronal regulation of cardiac behavior and modeling complex intercellular physiology.

UR - http://www.scopus.com/inward/record.url?scp=85008147322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008147322&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2016.05.002

DO - 10.1016/j.stem.2016.05.002

M3 - Article

C2 - 27320040

AN - SCOPUS:85008147322

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

ER -