Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines

被引：66

作者：

Mills, Jason A. ^{[1
,2
]}

Wang, Kai ^{[3
]}

Paluru, Prasuna ^{[1
,2
]}

Ying, Lei ^{[1
,2
]}

Lu, Lin ^{[1
,2
]}

Galvao, Aline M. ^{[1
,2
]}

Xu, Dongbin ^{[4
]}

Yao, Yu ^{[5
]}

Sullivan, Spencer K. ^{[5
]}

Sullivan, Lisa M. ^{[1
,2
]}

Mac, Helen ^{[1
,2
]}

Omari, Amel ^{[6
,7
]}

Jean, Jyh-Chang ^{[6
,7
]}

Shen, Steve ^{[8
,9
]}

Gower, Adam ^{[8
,9
]}

Spira, Avi ^{[8
,9
]}

Mostoslavsky, Gustavo ^{[6
,7
]}

Kotton, Darrell N. ^{[6
,7
]}

French, Deborah L. ^{[1
,2
]}

Weiss, Mitchell J. ^{[5
]}

Gadue, Paul ^{[1
,2
]}

机构：

[1] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Lab Med, Philadelphia, PA 19104 USA

[3] Univ So Calif, Zilkha Neurogenet Inst, Dept Psychiat & Prevent Med, Los Angeles, CA USA

[4] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[5] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA

[6] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[7] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA

[8] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA

[9] Boston Med Ctr, Boston, MA USA

来源：

BLOOD | 2013年 / 122卷 / 12期

基金：

美国国家卫生研究院;

关键词：

COPY NUMBER; DIFFERENTIATION; EXPRESSION;

D O I：

10.1182/blood-2013-02-484444

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2047 / 2051

页数：5

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