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The mitochondrial protein CHCHD2 primes the differentiation potential of human induced pluripotent stem cells to neuroectodermal lineages

Lookup NU author(s): Dr Lili Zhu, Dr Aurora Gomez Duran, Dr Gabriele Saretzki, Dr Katarzyna Tilgner, Dario Melguizo Sanchis, Dr George Anyfantis, Professor Patrick Chinnery, Professor Majlinda Lako, Professor Lyle Armstrong

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This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).


Abstract

Human induced pluripotent stem cells (hiPSC) utility is limited by variations in their ability to undergo lineage specific differentiation. We have undertaken a transcriptional comparison of human embryonic stem cell lines (hESC) and hiPSC lines and have shown that hiPSC are inferior in their ability to undergo neuroectodermal differentiation. Amongst the differentially expressed candidates between hESC and hiPSC, we identified a mitochondrial protein, CHCHD2, whose expression seems to correlate to neuroectodermal differentiation potential of pluripotent stem cells. We provide evidence that the hiPSC variability with respect to CHCHD2 expression and differentiation potential is caused by clonal variation during the reprogramming process and that CHCHD2 primes neuroectodermal differentiation of hESC and hiPSC through binding and sequestering SMDA4 to the mitochondria, resulting in suppression of the activity of the TGFβ signalling pathway. The potential utility of using CHCHD2 as a marker for assessing and comparing the hiPSC clonal and/or line differentiation potential provides a tool for large scale differentiation and hiPSC banking studies.


Publication metadata

Author(s): Zhu L, Gomez-Duran A, Saretzki G, Jin S, Tilgner K, Melguzo-Sanchis D, Anyfantis G, Al-Aama J, Vallier L, Chinnery P, Lako M, Armstrong L

Publication type: Article

Publication status: Published

Journal: Journal of Cell Biology

Year: 2016

Volume: 215

Issue: 2

Pages: 187-202

Print publication date: 24/10/2016

Online publication date: 17/10/2016

Acceptance date: 19/09/2016

ISSN (print): 0021-9525

ISSN (electronic): 1540-8140

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1083/jcb.201601061

DOI: 10.1083/jcb.201601061


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