Browse > Article
http://dx.doi.org/10.12717/DR.2016.20.2.149

Novel Function of Sprouty4 as a Regulator of Stemness and Differentiation of Embryonic Stem Cells  

Lee, Jae-Young (Dept. of Biomedical Science, College of Life Science, CHA University)
Park, Sunghyun (Dept. of Biomedical Science, College of Life Science, CHA University)
Kim, Kwang-Soo (Dept. of Biomedical Science, College of Life Science, CHA University)
Ko, Jeong-Jae (Dept. of Biomedical Science, College of Life Science, CHA University)
Lee, Soohong (Dept. of Biomedical Science, College of Life Science, CHA University)
Kim, Keun Pil (Dept. of Life Science, Chung-Ang University)
Park, Kyung-Soon (Dept. of Biomedical Science, College of Life Science, CHA University)
Publication Information
Development and Reproduction / v.20, no.2, 2016 , pp. 149-155 More about this Journal
Abstract
Sprouty (Spry) genes encode inhibitors of the receptor tyrosine kinase signaling cascade, which plays important roles in stem cells. However, the role of Spry4 in the stemness of embryonic stem cells has not been fully elucidated. Here, we used mouse embryonic stem cells (mESCs) as a model system to investigate the role of Spry4 in the stem cells. Suppression of Spry4 expression results in the decreases of cell proliferation, EB formation and stemness marker expression, suggesting that Spry4 activity is associated with stemness of mESCs. Teratoma assay showed that the cartilage maturation was facilitated in Spry4 knocked down mESCs. Our results suggest that Spry4 is an important regulator of the stemness and differentiation of mESCs.
Keywords
Sprouty4; Embryonic stem cell; Differentiation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Egan JE, Hall AB, Yatsula BA, Bar-Sagi D (2002) The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins. Proc Natl Acad Sci USA 99:6041-6046.   DOI
2 Felfly H, Klein OD (2013) Sprouty genes regulate proliferation and survival of human embryonic stem cells. Sci Rep 3:2277.   DOI
3 Chan RJ, Johnson SA, Li Y, Yoder MC, Feng GS (2003) A definitive role of Shp-2 tyrosine phosphatase in mediating embryonic stem cell differentiation and hematopoiesis. Blood 102:2074-2080.   DOI
4 de Maximy AA, Nakatake Y, Moncada S, Itoh N, Thiery JP, et al. (1999) Cloning and expression pattern of a mouse homologue of drosophila sprouty in the mouse embryo. Mech Dev 81:213-216.   DOI
5 Gross I, Bassit B, Benezra M, Licht JD (2001) Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem 276:46460-46468.   DOI
6 Ishida M, Ichihara M, Mii S, Jijiwa M, Asai N, et al. (2007) Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase. Cancer Sci 98:815-821.   DOI
7 Gross I, Armant O, Benosman S, de Aguilar JL, Freund JN, et al. (2007) Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival. Cell Death Differ 14:1802-1812.   DOI
8 Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow MA (1998) sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell 92:253-263.   DOI
9 Impagnatiello MA, Weitzer S, Gannon G, Compagni A, Cotten M, et al. (2001) Mammalian sprouty-1 and -2 are membrane-anchored phosphoprotein inhibitors of growth factor signaling in endothelial cells. J Cell Biol 152:1087-1098.   DOI
10 Jung JE, Moon SH, Kim DK, Choi C, Song J, et al. (2012) Sprouty1 regulates neural and endothelial differentiation of mouse embryonic stem cells. Stem Cells Dev 21:554-561.   DOI
11 Kramer S, Okabe M, Hacohen N, Krasnow MA, Hiromi Y (1999) Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila. Development 126:2515-2525.
12 Sasaki A, Taketomi T, Wakioka T, Kato R, Yoshimura A (2001) Identification of a dominant negative mutant of Sprouty that potentiates fibroblast growth factor- but not epidermal growth factor-induced ERK activation. J Biol Chem 276:36804-36808.   DOI
13 Kunath T, Saba-El-Leil MK, Almousailleakh M, Wray J, Meloche S, et al. (2007) FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development 134:2895-2902.   DOI
14 Lee J, Lee M, Moon B, Shim S, Fornace AJ, et al. (2009) Senescent growth arrest in mesenchymal stem cells is bypassed by Wip1-mediated downregulation of intrinsic stress signaling pathways. Stem Cells 27:1963-1975.   DOI
15 Leeksma OC, Van Achterberg TA, Tsumura Y, Toshima J, Eldering E, et al. (2002) Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1. Eur J Biochem 269:2546-2556.   DOI
16 Pelaez D, Arita N, Cheung HS (2012) Extracellular signalregulated kinase (ERK) dictates osteogenic and/or chondrogenic lineage commitment of mesenchymal stem cells under dynamic compression. Biochem Biophys Res Commun 417:1286-1291.   DOI
17 Rubin C, Litvak V, Medvedovsky H, Zwang Y, Lev S, et al. (2003) Sprouty fine-tunes EGF signaling through interlinked positive and negative feedback loops. Curr Biol 13:297-307.   DOI
18 Stavridis MP, Lunn JS, Collins BJ, Storey KG (2007) A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. Development 134:2889-2894.   DOI
19 Stavridis MP, Collins BJ, Storey KG (2010) Retinoic acid orchestrates fibroblast growth factor signalling to drive embryonic stem cell differentiation. Development 137:881-890.   DOI