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

Jason A. Mills, Kai Wang, Prasuna Paluru, Lei Ying, Lin Lu, Aline M. Galvão, Dongbin Xu, Y. Yao, Spencer K. Sullivan, Lisa M. Sullivan, Helen Mac, Amel Omari, Jyh Chang Jean, Steve Shen, Adam Gower, Avi Spira, Gustavo Mostoslavsky, Darrell N. Kotton, Deborah L. French, Mitchell J. WeissPaul Gadue

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2047-2051
Number of pages5
JournalBlood
Volume122
Issue number12
DOIs
StatePublished - 2013

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants RC2 HL101606 (M.J.W.), P30DK090969 (M.J.W.), U01 HL099656 (M.J.W., D.L.F., P.G.), and RC2HL101535 (D.N.K, G.M., P.G.).

Funding Information:
M.J.W. is a former Scholar of the Leukemia Lymphoma Society and The Jane Fishman Grinberg Professor of Pediatrics. This work was supported by National Institutes of Health grants RC2 HL101606 (M.J.W.), P30DK090969 (M.J.W.), U01 HL099656 (M.J.W., D.L.F., P.G.), and RC2HL101535 (D.N.K, G.M., P.G.).

Publisher Copyright:
© 2013 by The American Society of Hematology.

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