Cells; Central Nervous System Diseases; Nervous System; Stem Cells; Pluripotent Stem Cells; Embryonic Stem Cells; Induced Pluripotent Stem Cells; Neural Stem Cells; Psychiatry and Psychology
Stem Cell Center, Yale: Stem Cell Genetics
Overexpression of four factors (Oct4, Sox2, Klf4, Myc, or
Oct4, Sox2, Nanog, Lin28) reprogram somatic cells to become induced pluripotent
stem (iPS) cells. Reprogramming accompanies genetic and epigenetic changes, and
its molecular mechanism is still unknown. We recently showed that in iPS cells
the global DNA methylation status is close to that of human embryonic stem
(hES) cells, suggesting the epigenetic resetting during reprogramming.
Furthermore, we have showed the possible dissection of stages in reprogramming
through live cell imaging analysis.
We will investigate the molecular mechanism of genetic and epigenetic change during reprogramming. iPS cells show similar characteristics as hES cells, such as self-renewal and pluripotency, and provide an incredible resource for cell-based therapy, in vitro disease model and screening drugs.
Extensive Research Description
- Investigation of genetic and epigenetic regulation of reprogramming
- in vitro model of human neurodevelopmental disease
Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming.
Tanaka, Y., Hysolli, E., J. Su, Y. Xiang, K-.Y. Kim, M. Zhong, Y. Li, K Heydari, G. Euskirchen, M. P. Snyder, X. Pan, S. M. Weissman, and I.-H. Park (2015) Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming. Stem Cell Reports, 4:1125-39.
X Chromosome of Female Cells Shows Dynamic Changes in Status during Human Somatic Cell Reprogramming.
Kim, K.-Y., E. Hysolli, Y. Tanaka, B. Wang, Y.-W. Jung, X. Pan, S. M. Weissman, and I.-H. Park (2014) X Chromosome of Female Cells Shows Dynamic Changes in Status during Human Somatic Cell Reprogramming. Stem Cell Reports, 2:896-909.
Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2).
Tanaka, Y., K. Y. Kim, M. Zhong, X. Pan, S. M. Weissman, and I. H. Park (2014) Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2). Hum Mol Genet, 23:1045-55.
Pluripotent stem cell models of shwachman-diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction.
Tulpule, A., J. M. Kelley, M. W. Lensch, J. McPherson, I. H. Park, O. Hartung, T. Nakamura, T. M. Schlaeger, A. Shimamura and G. Q. Daley (2013). Pluripotent stem cell models of shwachman-diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell 12: 727-736.
Cellular reprogramming: a novel tool for investigating autism spectrum disorders.
Kim, K. Y., Y. W. Jung, G. J. Sullivan, L. Chung and I. H. Park (2012). Cellular reprogramming: a novel tool for investigating autism spectrum disorders. Trends Mol Med 18: 463-471.
Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome.
Kun-Yong Kim, Eriona Hysolli, In-Hyun Park. Neuronal maturation defect in induced pluripotent stem cells from Rett syndrome patients. Proc. Natl. Acad. Sci. 2011;108:14169-14174. (PMC3161557)
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients.
Agarwal, S., Y. H. Loh, E. M. McLoughlin, J. Huang, I. H. Park, J. D. Miller, H. Huo, M. Okuka, R. M. Dos Reis, S. Loewer, H. H. Ng, D. L. Keefe, et al. (2010). Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464: 292-296.
Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells.
Elayne M Chan*, Sutheera Ratanasirintrawoot*, In-Hyun Park*, Hongguang Huo, Philip D Manos, Junsung Rho, Yuin-Han Loh George Q. Daley and Thorsten M. Schlaeger (2009) Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nature Biotechnology. 27:1033-1037. (* contributed equally)
Hypo- and Hypermethylation of Tissue- and Cancer-related CpG Island Shores in Human Induced Pluripotent Stem (iPS) Cells.
Akiko Doi*, In-Hyun Park*, Bo Wen*, Peter Murakami, Dr. Rafael Irizarry, Brian Herb, Sabine Loewer, Thorsten Schlaeger, Justine Miller, Junsung Rho, George Q. Daley, Andrew P. Feinberg (2009), Hypo- and Hypermethylation of Tissue- and Cancer-related CpG Island Shores in Human Induced Pluripotent Stem (iPS) Cells. Nature Genetics. 41:1350-1353. (* contributed equally)
Disease-specific induced pluripotent stem cells.
In-Hyun Park, Natasha Arora , Hongguang Huo, Nimet Maherali, Tim Ahfeldt, Akiko Shimamura, M. William Lensch, Chad Cowan, Konrad Hochedlinger and George Q Daley (2008) Disease-specific induced pluripotent stem cells. Cell, 134:877-886.
Full List of PubMed Publications
- Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, Cakir B, Kim KY, Lombroso AP, Hwang SM, Zhong M, Stanley EG, Elefanty AG, Naegele JR, Lee SH, Weissman SM, Park IH: Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration. Cell Stem Cell. 2017 Jul 26; 2017 Jul 26. PMID: 28757360
- Han L, Wu HJ, Zhu H, Kim KY, Marjani SL, Riester M, Euskirchen G, Zi X, Yang J, Han J, Snyder M, Park IH, Irizarry R, Weissman SM, Michor F, Fan R, Pan X: Bisulfite-independent analysis of CpG island methylation enables genome-scale stratification of single cells. Nucleic Acids Res. 2017 Jun 2. PMID: 28126923
- Siller R, Dufour E, Lycke M, Wilmut I, Jung YW, Park IH, Sullivan GJ: Development of an inducible platform for intercellular protein delivery. Int J Pharm. 2017 Apr 30; 2017 Feb 28. PMID: 28254654
- Lee S, Park C, Han JW, Kim JY, Cho K, Kim EJ, Kim S, Lee SJ, Oh SY, Tanaka Y, Park IH, An HJ, Shin CM, Sharma S, Yoon YS: Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2. Circ Res. 2017 Mar 3; 2016 Dec 21. PMID: 28003219
- Yang J, Tanaka Y, Seay M, Li Z, Jin J, Garmire LX, Zhu X, Taylor A, Li W, Euskirchen G, Halene S, Kluger Y, Snyder MP, Park IH, Pan X, Weissman SM: Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors. Nucleic Acids Res. 2017 Feb 17. PMID: 28003475
- Park CY, Sung JJ, Choi SH, Lee DR, Park IH, Kim DW: Modeling and correction of structural variations in patient-derived iPSCs using CRISPR/Cas9. Nat Protoc. 2016 Nov; 2016 Oct 6. PMID: 27711053
- Liu R, Kim KY, Jung YW, Park IH: Dnmt1 regulates the myogenic lineage specification of muscle stem cells. Sci Rep. 2016 Oct 18; 2016 Oct 18. PMID: 27752090
- Hysolli E, Tanaka Y, Su J, Kim KY, Zhong T, Janknecht R, Zhou XL, Geng L, Qiu C, Pan X, Jung YW, Cheng J, Lu J, Zhong M, Weissman SM, Park IH: Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family. Stem Cell Reports. 2016 Jul 12; 2016 Jun 30. PMID: 27373925
- Greer CB, Tanaka Y, Kim YJ, Xie P, Zhang MQ, Park IH, Kim TH: Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery. Cell Rep. 2015 Nov 17; 2015 Nov 5. PMID: 26549458
- Lee BK, Shen W, Lee J, Rhee C, Chung H, Kim KY, Park IH, Kim J: Tgif1 Counterbalances the Activity of Core Pluripotency Factors in Mouse Embryonic Stem Cells. Cell Rep. 2015 Oct 6; 2015 Sep 24. PMID: 26411691
- Xiang Y, Kim KY, Gelernter J, Park IH, Zhang H: Ethanol upregulates NMDA receptor subunit gene expression in human embryonic stem cell-derived cortical neurons. PLoS One. 2015; 2015 Aug 12. PMID: 26266540
- Kwon YW, Paek JS, Cho HJ, Lee CS, Lee HJ, Park IH, Roh TY, Kang CM, Yang HM, Park YB, Kim HS: Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC. Biomaterials. 2015 Aug; 2015 May 15. PMID: 25956855
- Tanaka Y, Hysolli E, Su J, Xiang Y, Kim KY, Zhong M, Li Y, Heydari K, Euskirchen G, Snyder MP, Pan X, Weissman SM, Park IH: Transcriptome Signature and Regulation in Human Somatic Cell Reprogramming. Stem Cell Reports. 2015 Jun 9; 2015 May 21. PMID: 26004630
- Kim KY, Hysolli E, Tanaka Y, Wang B, Jung YW, Pan X, Weissman SM, Park IH: X Chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming. Stem Cell Reports. 2014 Jun 3; 2014 May 15. PMID: 24936474
- Jeon I, Choi C, Lee N, Im W, Kim M, Oh SH, Park IH, Kim HS, Song J: In Vivo Roles of a Patient-Derived Induced Pluripotent Stem Cell Line (HD72-iPSC) in the YAC128 Model of Huntington's Disease. Int J Stem Cells. 2014 May. PMID: 24921027
- Hysolli E, Park IH: Trivalent chromatin marks the way in. Cell Stem Cell. 2013 Nov 7. PMID: 24209756
- Dajani R, Koo SE, Sullivan GJ, Park IH: Investigation of Rett syndrome using pluripotent stem cells. J Cell Biochem. 2013 Nov. PMID: 23744605
- Cheng J, Guo S, Chen S, Mastriano SJ, Liu C, D'Alessio AC, Hysolli E, Guo Y, Yao H, Megyola CM, Li D, Liu J, Pan W, Roden CA, Zhou XL, Heydari K, Chen J, Park IH, Ding Y, Zhang Y, Lu J: An extensive network of TET2-targeting MicroRNAs regulates malignant hematopoiesis. Cell Rep. 2013 Oct 31; 2013 Oct 10. PMID: 24120864
- Siller R, Greenhough S, Park IH, Sullivan GJ: Modelling human disease with pluripotent stem cells. Curr Gene Ther. 2013 Apr. PMID: 23444871
- Pan X, Durrett RE, Zhu H, Tanaka Y, Li Y, Zi X, Marjani SL, Euskirchen G, Ma C, Lamotte RH, Park IH, Snyder MP, Mason CE, Weissman SM: Two methods for full-length RNA sequencing for low quantities of cells and single cells. Proc Natl Acad Sci U S A. 2013 Jan 8; 2012 Dec 24. PMID: 23267071
- Tanaka Y, Chung L, Park IH: Impact of retrotransposons in pluripotent stem cells. Mol Cells. 2012 Dec; 2012 Nov 6. PMID: 23135636
- Ge X, Ren Y, Bartulos O, Lee MY, Yue Z, Kim KY, Li W, Amos PJ, Bozkulak EC, Iyer A, Zheng W, Zhao H, Martin KA, Kotton DN, Tellides G, Park IH, Yue L, Qyang Y: Modeling supravalvular aortic stenosis syndrome with human induced pluripotent stem cells. Circulation. 2012 Oct 2; 2012 Aug 22. PMID: 22914687
- Kim KY, Jung YW, Sullivan GJ, Chung L, Park IH: Cellular reprogramming: a novel tool for investigating autism spectrum disorders. Trends Mol Med. 2012 Aug; 2012 Jul 6. PMID: 22771169
- Kim KY, Hysolli E, Park IH: Reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) using retroviral vector with GFP. J Vis Exp. 2012 Apr 3; 2012 Apr 3. PMID: 22491226
- Jung YW, Hysolli E, Kim KY, Tanaka Y, Park IH: Human induced pluripotent stem cells and neurodegenerative disease: prospects for novel therapies. Curr Opin Neurol. 2012 Apr. PMID: 22357218
- Zhou XL, Sullivan GJ, Sun P, Park IH: Humanized murine model for HBV and HCV using human induced pluripotent stem cells. Arch Pharm Res. 2012 Feb; 2012 Feb 28. PMID: 22370780
- Hysolli E, Jung YW, Tanaka Y, Kim KY, Park IH: The lesser known story of X chromosome reactivation: a closer look into the reprogramming of the inactive X chromosome. Cell Cycle. 2012 Jan 15; 2012 Jan 15. PMID: 22234239
- Kim KY, Hysolli E, Park IH: Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci U S A. 2011 Aug 23; 2011 Aug 1. PMID: 21807996
- Park IH: Five classic articles in somatic cell reprogramming. Yale J Biol Med. 2010 Sep. PMID: 20885901
- Park IH: DYS-HAC-iPS cells: the combination of gene and cell therapy to treat duchenne muscular dystrophy. Mol Ther. 2010 Feb. PMID: 20125163