Induction of reprogramming of human amniotic epithelial cells into iPS cells by overexpression of Yap, Oct4, and Sox2 through the activation of the Hippo-Yap pathway

Zhao,Yanhui; Fei,Xinfeng; Guo,Jianming; Zou,Gang; Pan,Weidong; Zhang,Jingju; Huang,Yongyi; Liu,Te; Cheng,Weiwei

doi:10.3892/etm.2017.4512

July-2017 Volume 14 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2017 Volume 14 Issue 1

Full Size Image

Article Open Access

Induction of reprogramming of human amniotic epithelial cells into iPS cells by overexpression of Yap, Oct4, and Sox2 through the activation of the Hippo-Yap pathway

Authors:
- Yanhui Zhao
- Xinfeng Fei
- Jianming Guo
- Gang Zou
- Weidong Pan
- Jingju Zhang
- Yongyi Huang
- Te Liu
- Weiwei Cheng
View Affiliations / Copyright

Affiliations: Department of Orthodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, P.R. China, Department of Ophthalmology, The Branch of Shanghai General Hospital, Shanghai 200081, P.R. China, Vascular Surgery Department, Xuanwu Hospital Capital Medical University, Beijing 100053, P.R. China, Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, P.R. China, Department of Neurology, Shuguang Hospital, Shanghai Traditional Chinese Medicine, Shanghai 201203, P.R. China, Laboratoire PROTEE, Bâtiment R, Université du Sud Toulon‑Var, 83957 La Garde Cedex, France, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai 200030, P.R. China

Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 199-206
|
Published online on: May 24, 2017

https://doi.org/10.3892/etm.2017.4512
Expand metrics +

Abstract

The present study has reported a novel method for producing induced pluripotent stem (iPS) cells. Primary human amniotic epithelial cells (HuAECs) were isolated from the amniotic membranes of pregnant women who received Cesarean sections. These cells were infected with retroviruses carrying octamer‑binding transcription factor 4 (Oct4), (sex determining region Y)‑box 2 (Sox2) and Yes‑associated protein (Yap) (OSY). Following in vitro culture for ~14 days, epithelial‑like HuAECs exhibited several iPS clone‑like cell colonies (OSY‑iPS). These cell clones presented positive alkaline phosphatase features and expressed high levels of embryonic stem cell‑like markers (Nanog homeobox, Sox2, Oct4, reduced expression protein 1, and SSES3/4). Additionally, epigenetic analysis results indicated that the methylation of CpG islands on endogenous Oct4 and Sox2 promoters was reduced in OSY‑iPS cells. Furthermore, the majority of the histone H3 at lysine 9 sites that interacted with the Oct4 and Sox2 promoters were acetylated, suggesting that the transcription activities of the above two transcription factors significantly increased. In vivo and in vitro induced differentiation experiments demonstrated that OSY‑iPS could develop into embryoid bodies in vitro, and express numerous cellular markers in the three germ layers. Furthermore, OSY‑iPS could form teratomas in immunodeficient mice. The pathological detection results suggest that these teratomas contain numerous types of cells from the three germ layers. However, the results from the quantitative polymerase chain reaction and western blot analyses suggest that the Hippo‑Yap signaling pathway was significantly activated in OSY‑iPS cells. In conclusion, a novel method for iPS induction was established in the present study. HuAECs were successfully induced to reprogram iPS cells through the introduction of OSY to activate the Hippo‑Yap signaling pathway.

View Figures

View References

1	Takahashi K and Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676. 2006. View Article : Google Scholar : PubMed/NCBI
2	Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K and Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar : PubMed/NCBI
3	Okita K, Ichisaka T and Yamanaka S: Generation of germline-competent induced pluripotent stem cells. Nature. 448:313–317. 2007. View Article : Google Scholar : PubMed/NCBI
4	Liu T, Zou G, Gao Y, Zhao X, Wang H, Huang Q, Jiang L, Guo L and Cheng W: High efficiency of reprogramming CD34+ cells derived from human amniotic fluid into induced pluripotent stem cells with Oct4. Stem Cells Dev. 21:2322–2332. 2012. View Article : Google Scholar : PubMed/NCBI
5	Wu J, Ocampo A and Belmonte JC Izpisua: Cellular metabolism and induced pluripotency. Cell. 166:1371–1385. 2016. View Article : Google Scholar : PubMed/NCBI
6	Zhang H, Pasolli HA and Fuchs E: Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc Natl Acad Sci USA. 108:pp. 2270–2275. 2011; View Article : Google Scholar : PubMed/NCBI
7	Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, et al: Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 150:780–791. 2012. View Article : Google Scholar : PubMed/NCBI
8	Hoa L, Kulaberoglu Y, Gundogdu R, Cook D, Mavis M, Gomez M, Gomez V and Hergovich A: The characterisation of LATS2 kinase regulation in Hippo-YAP signalling. Cell Signal. 28:488–497. 2016. View Article : Google Scholar : PubMed/NCBI
9	Qi YF, Yu J, Han W, Fan X, Qian H, Wei H, Tsai YH, Zhao J, Zhang W, Liu Q, et al: A splicing isoform of TEAD4 attenuates the Hippo-YAP signalling to inhibit tumour proliferation. Nat Commun. 7:ncomms118402016. View Article : Google Scholar : PubMed/NCBI
10	Lian I, Kim J, Okazawa H, Zhao J, Zhao B, Yu J, Chinnaiyan A, Israel MA, Goldstein LS, Abujarour R, et al: The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Gene Dev. 24:1106–1118. 2010. View Article : Google Scholar : PubMed/NCBI
11	Qin H, Blaschke K, Wei G, Ohi Y, Blouin L, Qi Z, Yu J, Yeh RF, Hebrok M and Ramalho-Santos M: Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming. Hum Mol Genet. 21:2054–2067. 2012. View Article : Google Scholar : PubMed/NCBI
12	Liu T, Cheng W, Huang Y, Huang Q, Jiang L and Guo L: Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression. Exp Cell Res. 318:424–434. 2012. View Article : Google Scholar : PubMed/NCBI
13	Hamanaka S, Yamaguchi T, Kobayashi T, Kato-Itoh M, Yamazaki S, Sato H, Umino A, Wakiyama Y, Arai M, Sanbo M, et al: Generation of germline-competent rat induced pluripotent stem cells. Plos One. 6:e220082011. View Article : Google Scholar : PubMed/NCBI
14	Lengner CJ: iPS cell technology in regenerative medicine. Ann NY Acad Sci. 1192:38–44. 2010. View Article : Google Scholar : PubMed/NCBI
15	Rowntree RK and McNeish JD: Induced pluripotent stem cells: Opportunities as research and development tools in 21st century drug discovery. Regen Med. 5:557–568. 2010. View Article : Google Scholar : PubMed/NCBI
16	Wang X, Zhao Y, Xiao Z, Chen B, Wei Z, Wang B, Zhang J, Han J, Gao Y, Li L, et al: Alternative translation of OCT4 by an internal ribosome entry site and its novel function in stress response. Stem cells. 27:1265–1275. 2009. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Induction of reprogramming of human amniotic epithelial cells into iPS cells by overexpression of Yap, Oct4, and Sox2 through the activation of the Hippo-Yap pathway

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles