Dissecting Diabetes/metabolic Disease Mechanisms Using Pluripotent Stem Cells and Genome Editing Tools

Overview

Journal Mol Metab

Specialty Cell Biology

Date 2015 Sep 29

PMID 26413465

Citations 10

Authors

Adrian Kee Keong Teo

Manoj K Gupta

Alessandro Doria

Rohit N Kulkarni

Affiliations

Soon will be listed here.

Abstract

Background: Diabetes and metabolic syndromes are chronic, devastating diseases with increasing prevalence. Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling. With recent rapid advances in genome editing tools, these cells can now be genetically manipulated with relative ease to study how genes and gene variants contribute to diabetes and metabolic syndromes.

Scope Of Review: We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases.

Major Conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease.

Citing Articles

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References

Yusa K, Rashid S, Strick-Marchand H, Varela I, Liu P, Paschon D . Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. 2011; 478(7369):391-4. PMC: 3198846. DOI: 10.1038/nature10424. View

Wang H, Jin Y, Reddy M, Podolsky R, Liu S, Yang P . Genetically dependent ERBB3 expression modulates antigen presenting cell function and type 1 diabetes risk. PLoS One. 2010; 5(7):e11789. PMC: 2909911. DOI: 10.1371/journal.pone.0011789. View

Hindorff L, Sethupathy P, Junkins H, Ramos E, Mehta J, Collins F . Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009; 106(23):9362-7. PMC: 2687147. DOI: 10.1073/pnas.0903103106. View

Tews D, Fischer-Posovszky P, Wabitsch M . Regulation of FTO and FTM expression during human preadipocyte differentiation. Horm Metab Res. 2010; 43(1):17-21. DOI: 10.1055/s-0030-1265130. View

Zou J, Mali P, Huang X, Dowey S, Cheng L . Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood. 2011; 118(17):4599-608. PMC: 3208277. DOI: 10.1182/blood-2011-02-335554. View

Sansbury F, Flanagan S, Houghton J, Shuixian Shen F, Al-Senani A, Habeb A . SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion. Diabetologia. 2012; 55(9):2381-5. DOI: 10.1007/s00125-012-2595-0. View

Soldner F, Laganiere J, Cheng A, Hockemeyer D, Gao Q, Alagappan R . Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell. 2011; 146(2):318-31. PMC: 3155290. DOI: 10.1016/j.cell.2011.06.019. View

Ran F, Hsu P, Lin C, Gootenberg J, Konermann S, Trevino A . Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 2013; 154(6):1380-9. PMC: 3856256. DOI: 10.1016/j.cell.2013.08.021. View

Osborn M, Starker C, McElroy A, Webber B, Riddle M, Xia L . TALEN-based gene correction for epidermolysis bullosa. Mol Ther. 2013; 21(6):1151-9. PMC: 3677309. DOI: 10.1038/mt.2013.56. View

10.

Lei F, Haque R, Xiong X, Song J . Directed differentiation of induced pluripotent stem cells towards T lymphocytes. J Vis Exp. 2012; (63):e3986. PMC: 3389997. DOI: 10.3791/3986. View

11.

Talchai C, Xuan S, Lin H, Sussel L, Accili D . Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell. 2012; 150(6):1223-34. PMC: 3445031. DOI: 10.1016/j.cell.2012.07.029. View

12.

Ding Q, Regan S, Xia Y, Oostrom L, Cowan C, Musunuru K . Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell. 2013; 12(4):393-4. PMC: 3925309. DOI: 10.1016/j.stem.2013.03.006. View

13.

Fu Y, Sander J, Reyon D, Cascio V, Joung J . Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014; 32(3):279-284. PMC: 3988262. DOI: 10.1038/nbt.2808. View

14.

Semple R, Savage D, Cochran E, Gorden P, ORahilly S . Genetic syndromes of severe insulin resistance. Endocr Rev. 2011; 32(4):498-514. DOI: 10.1210/er.2010-0020. View

15.

Gaj T, Gersbach C, Barbas 3rd C . ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013; 31(7):397-405. PMC: 3694601. DOI: 10.1016/j.tibtech.2013.04.004. View

16.

Hockemeyer D, Wang H, Kiani S, Lai C, Gao Q, Cassady J . Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol. 2011; 29(8):731-4. PMC: 3152587. DOI: 10.1038/nbt.1927. View

17.

Mussolino C, Morbitzer R, Lutge F, Dannemann N, Lahaye T, Cathomen T . A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res. 2011; 39(21):9283-93. PMC: 3241638. DOI: 10.1093/nar/gkr597. View

18.

Deltcheva E, Chylinski K, Sharma C, Gonzales K, Chao Y, Pirzada Z . CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature. 2011; 471(7340):602-7. PMC: 3070239. DOI: 10.1038/nature09886. View

19.

Teo A, Windmueller R, Johansson B, Dirice E, Njolstad P, Tjora E . Derivation of human induced pluripotent stem cells from patients with maturity onset diabetes of the young. J Biol Chem. 2013; 288(8):5353-6. PMC: 3581399. DOI: 10.1074/jbc.C112.428979. View

20.

Cerosaletti K, Buckner J . Protein tyrosine phosphatases and type 1 diabetes: genetic and functional implications of PTPN2 and PTPN22. Rev Diabet Stud. 2013; 9(4):188-200. PMC: 3740690. DOI: 10.1900/RDS.2012.9.188. View