Single-stranded DNA binding protein Ssbp3 induces differentiation of mouse embryonic stem cells into trophoblast-like cells

作者: Jifeng Liu , Xinlong Luo , Yanli Xu , Junjie Gu , Fan Tang

DOI: 10.1186/S13287-016-0340-1

关键词:

摘要: Intrinsic factors and extrinsic signals which control unlimited self-renewal developmental pluripotency in embryonic stem cells (ESCs) have been extensively investigated. However, a much smaller number of involved extra-embryonic trophoblast differentiation from ESCs studied. In this study, we investigated the role single-stranded DNA binding protein, Ssbp3, for induction trophoblast-like mouse ESCs. Gain- loss-of-function experiments were carried out through overexpression or knockdown Ssbp3 under culture conditions. Expression levels lineage markers detected by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses. The global gene expression profile Ssbp3-overexpressing was determined affymetrix microarray. Gene ontology pathway terms analyzed further validated qRT-PCR Western blotting. methylation status Elf5 promoter bisulfite sequencing. phenotype induced also evaluated teratoma formation early embryo injection assays. Forced upregulated lineage-associated genes, with cell being highest. contrast, depletion attenuated marker genes downregulation Oct4 treatment BMP4 bFGF Interestingly, profiling analysis indicated that did not significantly alter transcript pluripotency-associated transcription factors. Instead, promoted trophectoderm such as Cdx2 activated MAPK/Erk1/2 TGF-β pathways. Furthermore, reduced level generation teratomas internal hemorrhage, indicative presence cells. This study identifies regulator to differentiate into finding is helpful understand regulatory networks ESC lineages.

参考文章(42)
Jennifer Quinn, Tilo Kunath, Janet Rossant, Mouse trophoblast stem cells. Methods in molecular medicine. ,vol. 121, pp. 125- 148 ,(2006) , 10.1385/1-59259-983-4:123
Hitoshi Niwa, Jun-ichi Miyazaki, Austin G. Smith, Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature Genetics. ,vol. 24, pp. 372- 376 ,(2000) , 10.1038/74199
Heather J Lee, Rebecca A Hinshelwood, Toula Bouras, David Gallego-Ortega, Fátima Valdés-Mora, Katrina Blazek, Jane E Visvader, Susan J Clark, Christopher J Ormandy, None, Lineage Specific Methylation of the Elf5 Promoter in Mammary Epithelial Cells Stem Cells. ,vol. 29, pp. 1611- 1619 ,(2011) , 10.1002/STEM.706
Adrian Erlebacher, Kelly A. Price, Laurie H. Glimcher, Maintenance of mouse trophoblast stem cell proliferation by TGF-β/activin Developmental Biology. ,vol. 275, pp. 158- 169 ,(2004) , 10.1016/J.YDBIO.2004.07.032
A. Ralston, B. J. Cox, N. Nishioka, H. Sasaki, E. Chea, P. Rugg-Gunn, G. Guo, P. Robson, J. S. Draper, J. Rossant, Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2 Development. ,vol. 137, pp. 395- 403 ,(2010) , 10.1242/DEV.038828
Satoshi Tanaka, Tilo Kunath, Anna-Katerina Hadjantonakis, Andras Nagy, Janet Rossant, Promotion of Trophoblast Stem Cell Proliferation by FGF4 Science. ,vol. 282, pp. 2072- 2075 ,(1998) , 10.1126/SCIENCE.282.5396.2072
Dashzeveg Bayarsaihan, SSDP1 gene encodes a protein with a conserved N-terminal FORWARD domain Biochimica et Biophysica Acta. ,vol. 1599, pp. 152- 155 ,(2002) , 10.1016/S1570-9639(02)00376-X
Y. Jin, X. L. Xu, M.-C. W. Yang, F. Wei, T.-C. Ayi, A. M. Bowcock, R. Baer, Cell cycle-dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 12075- 12080 ,(1997) , 10.1073/PNAS.94.22.12075