Browse > Article

Up-regulation of Pluripotency-related Genes in Human Amniotic Fluid-derived Stem Cells by ESRRB Conjugated with Cell-Penetrating Peptide  

Jo, Jung-Hyun (Dept. of Biomedical Science, College of Life Science, CHA University)
Lee, Yu-Sun (Dept. of Biomedical Science, College of Life Science, CHA University)
Oh, Mi-Hee (Dept. of Biology, College of Natural Science, Sungshin Women's University)
Ko, Jung-Jae (Dept. of Biomedical Science, College of Life Science, CHA University)
Cheon, Yong-Pil (Dept. of Biology, College of Natural Science, Sungshin Women's University)
Lee, Dong-Ryul (Dept. of Biomedical Science, College of Life Science, CHA University)
Publication Information
Development and Reproduction / v.14, no.4, 2010 , pp. 243-251 More about this Journal
Abstract
ESRRB (Estrogen related receptor $\beta$) is an orphan receptor, and have a role on maintaining the undifferentiated state and self-renewal of pluripotent stem cell as a transcription factor which regulates the expression of OCT4 and NANOG genes. Also, Feng et al. (2009) reported that Esrrb, Oct4 and Sox2 could induce pluripotent stem cell from somatic cells. The aim of the present study was to develop the direct delivery system of human ESRRB protein into human amniotic fluid-derived stem cells (AFSCs) and to analyze the effect of ESRRB on the regulation of pluripotency-related genes. Human ESRRB has three isoforms arisen by alternative splicing. We cloned short-form ESRRB and made a fusion protein of ESRRB and R7 for an efficient protein transfer to cell. R7 as cell-penetrating peptide(CPP) can help to transfer ESRRB into cells. R7-ESRRB-His6 protein was observed in the cytoplasm and nuclei within 5 hours after treatment. Also, we could observe R7-ESRRB-His6 protein only in the nuclei within 24 hours. Realtime PCR showed that ESRRB increased expression of OCT4 and NANOG as well as SOX2 gene. Therefore, we demonstrated that R7-ESRRB-His6 proteins were efficiently transferred into the nuclei of AFSCs and work well as a possible transcription factor.
Keywords
ESRRB; Cell-penetrating peptide; Pluripotent-regulating genes; Human amniotic fluid-derived stem cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Giguere V, Yang N, Segui P, Evans RM (1988) Identification of a new class of steroid hormone receptors. Nature 331:91-94.   DOI   ScienceOn
2 O'Malley J, Woltjen K, Kaji K (2009) New strategies to generate induced pluripotent stem cells. Curr Opin Biotech. 20:1-6.   DOI   ScienceOn
3 Zhang X, Zhang J, Wang T, Esteban MA, Pei D (2008) Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells. J Biol Chem 283:35825-35833.   DOI   ScienceOn
4 Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.   DOI   ScienceOn
5 van den Berg DL, Zhang W, Yates A, Engelen E, Takacs K, Bezstarosti K, Demmers J, Chambers I, Poot RA (2008) Estrogen-related receptor beta interacts with Oct4 to positively regulate Nanog gene expression. Mol Cell Biol 28:5986-5995.   DOI   ScienceOn
6 Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM (1999) Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2. Mol Endocrinol 13:2151-2162.   DOI   ScienceOn
7 Yu S, Wong YC, Wang XH, Ling MT, Ng CF, Chen S, Chan FL (2008) Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in vivo growth of prostate cancer cells via p21 (WAF1/CIP1) induction and as a potential therapeutic target in prostate cancer. Oncogene 27:3313-3328.   DOI   ScienceOn
8 Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Scholer HR, Duan L, Ding S (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381-384.   DOI   ScienceOn
9 Zhou W, Liu Z, Wu J, Liu JH, Hyder SM, Antoniou E, Lubahn DB (2006) Identification and characterization of two novel splicing isoforms of human estrogen-related receptor beta. J Clin Endocrinol Metab 91:569-579.   DOI
10 Bombail V, MacPherson S, Critchley HO, Saunders PT (2008) Estrogen receptor related beta is expressed in human endometrium throughout the normal menstrual cycle. Hum Reprod 23:2782-2790.   DOI   ScienceOn
11 Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133:1106-1117.   DOI   ScienceOn
12 Feng B, Jiang J, Kraus P, Ng JH, Heng JC, Chan YS, Yaw LP, Zhang W, Loh YH, Han J, Vega VB, Cacheux-Rataboul V, Lim B, Lufkin T, Ng HH (2009) Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11 197-203.   DOI   ScienceOn
13 Frankel AD, Pabo CO (1988) Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55:1189-1193.   DOI   ScienceOn
14 Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472-476.   DOI   ScienceOn
15 Onishi A, Peng GH, Poth EM, Lee DA, Chen J, Alexis U, de Melo J, Chen S, Blackshaw S (2010) The orphan nuclear hormone receptor ERRbeta controls rod photoreceptor survival. Proc Natl Acad Sci USA 107:11579-11584   DOI   ScienceOn
16 Lee JE, Kang MS, Park MH, Shim SH, Yoon TK, Chung HM, Lee DR (2010) Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy : implications of HLA and ABO genotypes. Cell Transplant June 29 [Epub ahead of print]   DOI   ScienceOn