本實驗室的研究目標在探討成體幹細胞維持幹性(stemness)及進行分化(differentiation)的分子機制。人類胎盤為絨毛組織(villi)所構成,組織中的滋養幹細胞(trophoblast stem cells, TS cells)可分化為多核的合體滋養細胞(multinucleate syncytiotrophoblasts, STBs)及移行的外絨毛滋養細胞(migratory extravillous trophoblasts, EVTs)。另外,絨毛組織中的細胞滋養細胞(cytotrophoblasts, CTBs)具有類似TS細胞的特性。GCM1轉錄因子主宰STB 及EVT的分化,其活性受到不同訊息傳遞路徑的正、反向控制。藉由調整這些路徑,我們成功地將CTBs轉分化為TS細胞。胎盤負責母親與胎兒之間養分及氣體的交換。功能不健全的胎盤導致子癇前兆(preeclampsia, PE)及子宮內生長遲緩(intrauterine growth retardation, IUGR)等症狀,使胎兒在懷孕過程中處於營養不良的狀況,將來在成人階段也會有冠狀動脈、高血壓、中風及第二型糖尿病的高好發機率。我們當前利用TS細胞研究(1)維持其幹性的上游調控因子,(2)進一步誘導其為多能性的幹細胞以提供自體細胞療法及(3)研究TS細胞分化缺陷與PE及IUGR成因的關連性。
A novel cAMP/Epac1/CaMKI signaling cascade promotes GCM1 desumoylation and placental cell fusion.
Chang, C.W.; Chang, G.D.; Chen, H.
Mol. Cell. Biol. (2011)
Dual-specificity phosphatase 23 mediates GCM1 dephosphorylation and activation.
Lin, F.Y.; Chang, C.W.; Cheong, M.L.; Chen, H.C.; Lee, D.Y.; Chang, G.D.; Chen, H.
Nucleic Acids Res. (2011)
GCM1 Regulation of the Expression of Syncytin-2 and Its Cognate Receptor MFSD2A in Placenta.
Liang, C.Y.; Wang, L.J.; Chen, C.P.; Chen, L.F.; Chen, Y.H.; Chen, H.
Biol. Reprod. (2010)
Gcm Protein Degradation Suppresses Proliferation of Glial Progenitors.
Ho, M.; Chen, H.; Chen, M.; Jacques, C.; Giangrande, A.; and Chien, C.T.
Proc. Natl. Acad. Sci. USA (2009)
Mechanism of Hypoxia-Induced GCM1 Degradation: Implications for the Pathogenesis of Preeclampsia.
Chiang MH, Liang FY, Chen CP, Chang CW, Cheong ML, Wang LJ, Liang CY, Lin FY, Chou CC, Chen H
J. Biol. Chem. (2009)
Functional Characterization of the Human Placental Fusogenic Membrane Protein Syncytin 2.
Chen, C.P.; Chen, L.F.; Yang, S.R.; Chen, C.Y.; Ko, C.C.; Chang, G.D.; Chen, H.
Biol. Reprod. (2008)
Ubiquitin-Conjugating Enzyme UBE2D2 Is Responsible for F-Box and WD Repeat Domain Containing 2-Mediated Human Glial Cell Missing Homolog 1 Ubiquitination and Degradation.
Chiang, M.H.; Chen, L.F.; Chen, H.
Biol. Reprod. (2008)
Small Ubiquitin-like Modifier Modification Regulates the DNA Binding Activity of Glial Cell Missing Drosophila Homolog a.
Chou, C.C.; Chang, C.W.; Liu J.H.; Hsiao, C.D.; Chen, H.
J. Biol. Chem. (2007)
Thiazolidinediones modulate the expression of beta-catenin and other cell-cycle regulatoryproteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor gamma.
Wei, S.; Lin, L.F.; Yang, C.C.; Wang, Y.C.; Chang, G.D.; Chen, H.; Chen, C.S.
Mol. Pharm. (2007)
Histone Deacetylase 3 Binds to and Regulates the GCMa Transcription Factor.
Chuang, H.C.; Chang, C.W.; Chang, G.D.; Yao, T.P.; Chen, H.
Nucleic Acids Res. (2006)