Partial Reprogramming of Pluripotent Stem Cell-Derived Cardiomyocytes into Neurons View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Wenpo Chuang, Arun Sharma, Praveen Shukla, Guang Li, Moritz Mall, Kuppusamy Rajarajan, Oscar J. Abilez, Ryoko Hamaguchi, Joseph C. Wu, Marius Wernig, Sean M. Wu

ABSTRACT

Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD. We found that CMs adopted neuronal morphologies as early as day 3 post-transduction while still retaining a CM gene expression profile. At week 1 post-transduction, we found that reprogrammed CMs expressed neuronal markers such as Tuj1, Map2, and NCAM. At week 3 post-transduction, mature neuronal markers such as vGlut and synapsin were observed. With single-cell qPCR, we temporally examined CM gene expression and observed increased expression of neuronal markers Dcx, Map2, and Tubb3. Patch-clamp analysis confirmed the neuron-like electrophysiological profile of reprogrammed CMs. This study demonstrates that PSC-CMs are amenable to partial neuronal conversion, yielding a population of cells exhibiting features of both neurons and CMs. More... »

PAGES

44840

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep44840

DOI

http://dx.doi.org/10.1038/srep44840

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084132715

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28327614


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