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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 LakoORCiD, Professor Lyle Armstrong
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).
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.
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
Date deposited: 29/10/2016
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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