Genetic Background Drives Transcriptional Variation in Human Induced Pluripotent Stem Cells

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Human induced pluripotent stem (hiPS) cells are a potentially powerful model system for studying human disease and development, and a resource for personalized medicine. However, it has been reported that hiPS cells exhibit substantial heterogeneity which could limit their use as model systems. Clearly, knowledge of the source of heterogeneity is key for deeper understanding of the use of human iPS cells for basic and therapeutic applications. One source of this heterogeneity has been presumed to be “memory” of the adult somatic cell from which the hIPS cells were derived, but the evidence to support this view is scant. We have generated a set of human iPS cells from a set of somatic cell types from different donors. Our study shows that cell lines from different somatic sources but from the same donor (i.e. with the same genome) are more similar than cell lines isolated from the same tissue type but from different donors. Once genetic changes are accounted for, all aspects of gene expression, including mRNA levels, splicing and imprinting are highly similar between iPS cells derived from different human tissues. Thus, most of the previously described transcriptional variation between cell lines is likely to be genetic in origin.

Vyšlo v časopise: Genetic Background Drives Transcriptional Variation in Human Induced Pluripotent Stem Cells. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004432
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004432

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Zdroje

1. TakahashiK, TanabeK, OhnukiM, NaritaM, IchisakaT, et al. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131: 861–872.

2. WuS, HochedlingerK (2011) Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nature Cell Biology 13: 497–505.

3. LundR, NarvaE, LahesmaaR (2012) Genetic and epigenetic stability of human pluripotent stem cells. Nature Reviews Genetics 13: 732–744.

4. ChinM, MasonM, XieW, VoliniaS, SingerM, et al. (2009) Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5: 111–123.

5. KimK, DoiA, WenB, NgK, ZhaoR, et al. (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467: 285–290.

6. KimK, ZhaoR, DoiA, NgK, UnternaehrerJ, et al. (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nature Biotechnology 29: 1117–1119.

7. ListerR, PelizzolaM, KidaY, HawkinsR, NeryJ, et al. (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471: 68–73.

8. PoloJ, LiuS, FigueroaM, KulalertW, EminliS, et al. (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nature Biotechnology 28: 848–855.

9. OhiY, QinH, HongC, BlouinL, PoloJ, et al. (2011) Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nature Cell Biology 13: 541–549.

10. Bar-NurO, RussH, EfratS, BenvenistyN (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9: 17–23.

11. SkellyD, RonaldJ, AkeyJ (2009) Inherited variation in gene expression. Annual Review of Genomics and Human Genetics 10: 313–332.

12. BellJ, PaA, PickrellJ, GaffneyD, Pique-RegR, et al. (2011) DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biology 12: R10.

13. GibbsJ, van der BrugM, HernandezD, TraynorB, NallsM, et al. (2010) Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain. PLoS Genetics 6: e1000952.

14. LangmeadB, SalzbergS (2012) Fast gapped-read alignment with Bowtie 2. Nature Methods 9: 357–359.

15. TrapnellC, PachterL, SalzbergS (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105–1111.

16. EfroniS, DuttaguptaR, ChengJ, DehghaniH, HoeppnerD, et al. (2008) Global transcription in pluripotent embryonic stem cells. Cell Stem Cell 2: 437–447.

17. MarchettoM, YeoG, KainohanaO, MarsalaM, GageF, et al. (2009) Transcriptional signature and memory retention of human-induced pluripotent stem cells. PloS One 4: e7076.

18. GhoshZ, WilsonK, WuY, HuS, QuertermousT, et al. (2010) Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells. PloS one 5: e8975.

19. AndersS, HuberW (2010) Differential expression analysis for sequence count data. Genome Biology 11: R106.

20. VeyrierasJ-B, KudaravalliS, KimS, DermitzakisE, GiladY, et al. (2008) High-resolution mapping of expression-QTLs yields insight into human gene regulation. PLoS Genetics 4: e1000214.

21. PoloJ, AnderssenE, WalshR, SchwarzB, NefzgerC, et al. (2012) A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells. Cell 151: 1617–1632.

22. TrapnellC, WilliamsB, PerteaG, MortazaviA, KwanG, et al. (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology 28: 511–515.

23. KatzY, WangE, AiroldiE, BurgeC (2010) Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nature Methods 7: 1009–1015.

24. PickM, StelzerY, Bar-NurO, MaysharY, EdenA, et al. (2009) Clone- and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells 27: 2686–2690.

25. BrowningB, BrowningS (2009) A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals. American Journal of Human Genetics 84: 210–223.

26. GaffneyD (2013) Global properties and functional complexity of human gene regulatory variation. PLoS Genetics 9: e1003501.

27. LappalainenT, SammethM, FriedlanderM, t HoenP, MonlongJ, et al. (2013) Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501: 506–511.

28. WangA, HuangK, ShenY, XueZ, CaiC, et al. (2011) Functional modules distinguish human induced pluripotent stem cells from embryonic stem cells. Stem Cells and Development 20: 1937–1950.

29. NewmanA, CooperJ (2010) Lab-specific gene expression signatures in pluripotent stem cells. Cell Stem Cell 7: 258–262.

30. KajiwaraM, AoiT, OkitaK, TakahashiR, InoueH, et al. (2012) Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America 109: 12538–12543.

31. GuentherM, FramptonG, SoldnerF, HockemeyerD, MitalipovaM, et al. (2010) Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell 7: 249–257.

32. BockC, KiskinisE, VerstappenG, GuH, BoultingG, et al. (2011) Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144: 439–452.

33. YamanakaS (2012) Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10: 678–684.

34. KimD, PerteaG, TrapnellC, PimentelH, KelleyR, et al. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biology 14: R36.

35. PriceAL, PattersonNJ, PlengeRM, WeinblattME, ShadickNA, et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38: 904–909.