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academies
17
th
International Conference on
4
th
International Conference on
NEUROLOGY AND NEUROSCIENCE
&
MENTAL HEALTH AND PRIMARY CARE
October 16-18, 2017 | Toronto, Canada
J Neurol Neurorehabil Res 2017 | Volume 2 Issue 3
Early changes in neuronal cells derived from isogeneic pair of normal and genomic edited Alzheimer’s
disease (AD)-iPSCs
John Yu
1, 2
, Ming-Wei Kuo
1
and
Sheng-Wen Chen
1
1
Linkou Chang Gung Memorial Hospital, Taiwan
2
Academia Sinica, Taiwan
W
hile patient-derived AD-induced pluripotent stem cells
(iPSCs) can recapitulate AD phenotypes, the lack of
isogenic pair of normal and AD-iPSC with identical genetic
background for comparison may impede the detailed
analysis of subtle pathophysiological changes in early stage
of disease. We had developed a robust MS-based proteomic
platform to explore these early changes of pathogenesis
by comparing the protein expression in isogeneic pair of
normal and AD-iPSCs derived neuron cells. In proteome-
wide label-free quantitation of the isogenic pair-derived
neural progenitor and neuron cells, the changes of proteome
context are proportional to the neuronal differentiation,
when compared to their iPSC state, as indicated by the
Pearson’s correlation coefficient of triplicate datasets. We
then explored the changes caused by D678H mutation in
amyloid-beta precursor protein (APP) by comparing the
proteome between the isogenic pair during their neuronal
differentiation process. Our results suggested that the
differential display of proteome between WT and AD is
more significant at the state of mature neuron at day 15
(NM15). Using Perseus to identify the statistically different
expressed proteins between the isogenic pair of 71-WT-
NM15 and 71-AD-NM15, we found 299 proteins with
significant difference based on the significance criteria of
false discovery rate (FDR) 0.01 and small positive constant
(So). The 299 proteins were subjected to cluster analysis
and presented by the heatmap, which revealed the up- or
down-regulation of protein cluster caused by D678H-APP.
Launching from these MS-based technology platform, we
are now focusing on finding potential pathological/diagnosis
markers for AD. We selected candidate genes from these
299 proteins and confirm the changes of mRNA expression
during neuron differentiation in the iPSC pair. We also found
that alterations of these gene expressions in iPSC lead to
changes of amyloid 40/42, characteristics of AD phenotypes.
Speaker Biography
John Yu is Distinguished Chair Professor/Director at Institute of Stem Cell/Translational
Cancer Research, CGMH. He is also Distinguished Visiting Research Fellow at Institute
of Cellular and Organismic Biology, Academia Sinica, and was the Director for the same
Institute (2002-2009). He is the founding President for Taiwan Society for Stem Cell
Research. He was elected to serve in ISSCR Committees (USA), the Steering Committee
of Asia-Pacific Stem Cell Network, and Advisor for Stem Cell Biology, Kumamoto Univ.
He was the Director of Exp. Hematology (1998-2002) at Scripps Research Institute,
USA. He has received an Established Investigatorship Award from American Heart
Assoc. and many other awards.
e
:johnyu@cgmh.org.tw