Integrity of Induced Pluripotent Stem Cell (iPSC) Derived Megakaryocytes as Assessed by Genetic and Transcriptomic Analysis

被引：7

作者：

Kammers, Kai ^{[1
,2
]}

Taub, Margaret A. ^{[2
]}

Ruczinski, Ingo ^{[2
]}

Martin, Joshua ^{[3
]}

Yanek, Lisa R. ^{[3
]}

Frazee, Alyssa ^{[2
]}

Gao, Yongxing ^{[4
,5
]}

Hoyle, Dixie ^{[4
,5
]}

Faraday, Nauder ^{[3
]}

Becker, Diane M. ^{[3
]}

Cheng, Linzhao ^{[4
,5
]}

Wang, Zack Z. ^{[4
,5
]}

Leek, Jeff T. ^{[2
]}

Becker, Lewis C. ^{[3
]}

Mathias, Rasika A. ^{[3
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Biostat & Bioinformat,Sidney Kimmel Comprehen, Baltimore, MD 21205 USA

[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[3] Johns Hopkins Sch Med, GeneSTAR Res Program, Baltimore, MD 21205 USA

[4] Johns Hopkins Sch Med, Div Hematol, Baltimore, MD USA

[5] Johns Hopkins Sch Med, Inst Cell Engn, Baltimore, MD USA

来源：

PLOS ONE | 2017年 / 12卷 / 01期

关键词：

COPY NUMBER; GENOMIC INSTABILITY; HERITABILITY; AGGREGATION; ACTIVATION; ASPIRIN; VARIANT; TOOL;

D O I：

10.1371/journal.pone.0167794

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Previously, we have described our feeder-free, xeno-free approach to generate megakaryo-cytes (MKs) in culture from human induced pluripotent stem cells (iPSCs). Here, we focus specifically on the integrity of these MKs using: (1) genotype discordance between parent cell DNA to iPSC cell DNA and onward to the differentiated MK DNA; (2) genomic structural integrity using copy number variation (CNV); and (3) transcriptomic signatures of the derived MK lines compared to the iPSC lines. We detected a very low rate of genotype discordance; estimates were 0.0001%-0.01%, well below the genotyping error rate for our assay (0.37%). No CNVs were generated in the iPSCs that were subsequently passed on to the MKs. Finally, we observed highly biologically relevant gene sets as being upregulated in MKs relative to the iPSCs: platelet activation, blood coagulation, megakaryocyte development, platelet formation, platelet degranulation, and platelet aggregation. These data strongly support the integrity of the derived MK lines.

引用

页数：16

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