Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Mills JA,Wang K,Paluru P,Ying L,Lu L,Galvão AM,Xu D,Yao Y,Sullivan SK,Sullivan LM,Mac H,Omari A,Jean JC,Shen S,Gower A,Spira A,Mostoslavsky G,Kotton DN,French DL,Weiss MJ,Gadue Pdoi
10.1182/blood-2013-02-484444subject
Has Abstractpub_date
2013-09-19 00:00:00pages
2047-51issue
12eissn
0006-4971issn
1528-0020pii
blood-2013-02-484444journal_volume
122pub_type
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