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Page 27

Notes:

allied

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