Identification of Epigenetic Factor Proteins Expressed in Human Embryonic Stem Cell-Derived Trophoblasts and in Human Placental Trophoblasts
Autor: | Timothy S. Collier, Shan M. Randall, Adam Mischler, Karen F. Dorman, Balaji M. Rao, Kim A. Boggess, David C. Muddiman, Prasenjit Sarkar |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Epigenomics Cellular differentiation Placenta Quantitative proteomics Human Embryonic Stem Cells Gene Expression Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Pregnancy Stable isotope labeling by amino acids in cell culture medicine Humans Epigenetics DNA (Cytosine-5-)-Methyltransferases reproductive and urinary physiology Trophoblast Cell Differentiation General Chemistry Embryonic stem cell Molecular biology Trophoblasts 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Proteome Female biological phenomena cell phenomena and immunity Transcription Factors |
Zdroj: | Journal of proteome research. 15(8) |
ISSN: | 1535-3907 |
Popis: | Human embryonic stem cells (hESCs) have been used to derive trophoblasts through differentiation in vitro. Intriguingly, mouse ESCs are prevented from differentiation to trophoblasts by certain epigenetic factor proteins such as Dnmt1, thus necessitating the study of epigenetic factor proteins during hESC differentiation to trophoblasts. We used stable isotope labeling by amino acids in cell culture and quantitative proteomics to study changes in the nuclear proteome during hESC differentiation to trophoblasts and identified changes in the expression of 30 epigenetic factor proteins. Importantly, the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B were downregulated. Additionally, we hypothesized that nuclear proteomics of hESC-derived trophoblasts may be used for screening epigenetic factor proteins expressed by primary trophoblasts in human placental tissue. Accordingly, we conducted immunohistochemistry analysis of six epigenetic factor proteins identified from hESC-derived trophoblasts-DNMT1, DNMT3B, BAF155, BAF60A, BAF57, and ING5-in 6-9 week human placentas. Indeed, expression of these proteins was largely, though not fully, consistent with that observed in 6-9 week placental trophoblasts. Our results support the use of hESC-derived trophoblasts as a model for placental trophoblasts, which will enable further investigation of epigenetic factors involved in human trophoblast development. |
Databáze: | OpenAIRE |
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