Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines.
Induced pluripotent stem cells (iPSCs) hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained. We created and analyzed 3 separate iPSC clones from fibroblasts of 3 different normal individuals using a standardized approach that included excision of integrated reprogramming genes by Cre-Lox mediated recombination. Gene expression profiling and hematopoietic differentiation assays showed that independent lines from the same individual were generally more similar to one another than those from different individuals. However, one iPSC line (WT2.1) exhibited a distinctly different gene expression, proliferation rate, and hematopoietic developmental potential relative to all other iPSC lines. This "outlier" clone also acquired extensive copy number variations (CNVs) during reprogramming, which may be responsible for its divergent properties. Our data indicate how inherent and acquired genetic differences can influence iPSC properties, including hematopoietic potential.
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA;
Jason A
JA
Mills
Kai
K
Wang
Prasuna
P
Paluru
Lei
L
Ying
Lin
L
Lu
Aline M
AM
Galvão
Dongbin
D
Xu
Yu
Y
Yao
Spencer K
SK
Sullivan
Lisa M
LM
Sullivan
Helen
H
Mac
Amel
A
Omari
Jyh-Chang
JC
Jean
Steve
S
Shen
Adam
A
Gower
Avi
A
Spira
Gustavo
G
Mostoslavsky
Darrell N
DN
Kotton
Deborah L
DL
French
Mitchell J
MJ
Weiss
Paul
P
Gadue
D002454:Cell Differentiation; D002460:Cell Line; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018740:Genetic Heterogeneity; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D034061:Thrombopoiesis / Q000235:genetics