Embryonic stem cell-specific miR302-367 cluster: human gene structure and functional characterization of its core promoter.
Alicia Barroso-delJesus,Cristina Romero-López,Gema Lucena-Aguilar,Gema Lucena-Aguilar,Gustavo J. Melen,Laura Sánchez,Gertrudis Ligero,Alfredo Berzal-Herranz,Pablo Menendez +8 more
TLDR
This study represents the first identification, characterization, and functional validation of a human miRNA promoter in stem cells and opens up new avenues to further investigate the upstream transcriptional regulation of the miR302-367 cluster.Abstract:
MicroRNAs (miRNAs) play a central role in the regulation of multiple biological processes including the maintenance of stem cell self-renewal and pluripotency. Recently, the miRNA cluster miR302-367 was shown to be differentially expressed in embryonic stem cells (ESCs). Unfortunately, very little is known about the genomic structure of miRNA-encoding genes and their transcriptional units. Here, we have characterized the structure of the gene coding for the human miR302-367 cluster. We identify the transcriptional start and functional core promoter region which specifically drives the expression of this miRNA cluster. The promoter activity depends on the ontogeny and hierarchical cellular stage. It is functional during embryonic development, but it is turned off later in development. From a hierarchical standpoint, its activity decays upon differentiation of ESCs, suggesting that its activity is restricted to the ESC compartment and that the ESC-specific expression of the miR302-367 cluster is fully conferred by its core promoter transcriptional activity. Furthermore, algorithmic prediction of transcription factor binding sites and knockdown studies suggest that ESC-associated transcription factors, including Nanog, Oct3/4, Sox2, and Rex1 may be upstream regulators of miR302-367 promoter. This study represents the first identification, characterization, and functional validation of a human miRNA promoter in stem cells. This study opens up new avenues to further investigate the upstream transcriptional regulation of the miR302-367 cluster and to dissect how these miRNAs integrate in the complex molecular network conferring stem cell properties to ESCs.read more
Citations
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Exosomal cell-to-cell transmission of alpha synuclein oligomers
Karin M Danzer,Karin M Danzer,Lisa R. Kranich,Wolfgang Ruf,Ozge Cagsal-Getkin,Ashley R. Winslow,Liya Zhu,Charles R. Vanderburg,Pamela J. McLean,Pamela J. McLean +9 more
TL;DR: The data suggest that αsyn may be secreted via different secretory pathways, and hypothesize that exosome-mediated release of αsyn oligomers is a mechanism whereby cells clear toxic α synuclein oligomers when autophagic mechanisms fail to be sufficient.
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HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells
Julie Mathieu,Zhan Zhang,Wenyu Zhou,Amy Wang,John M. Heddleston,Claudia M A Pinna,Alexis Hubaud,Bradford M. Stadler,Michael Choi,Merav Bar,Muneesh Tewari,Alvin Y. Liu,Robert L. Vessella,Robert C. Rostomily,Donald E. Born,Marshall S. Horwitz,Carol B. Ware,C. Anthony Blau,Michele A. Cleary,Jeremy N. Rich,Hannele Ruohola-Baker +20 more
TL;DR: Hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT4, NANOG, SOX2, KLF4, cMYC, and microRNA-302 in 11 cancer cell lines.
Journal ArticleDOI
The Histone Demethylases Jhdm1a/1b Enhance Somatic Cell Reprogramming in a Vitamin-C-Dependent Manner
Tao Wang,Keshi Chen,Xiaoming Zeng,Jianguo Yang,Yun Wu,Xi Shi,Baoming Qin,Lingwen Zeng,Miguel A. Esteban,Guangjin Pan,Duanqing Pei +10 more
TL;DR: A role for H3K36me2/3 in cell fate determination is revealed and a link between histone demethylases and vitamin-C-induced reprogramming is established and established.
Journal ArticleDOI
Regulation of Stem Cell Pluripotency and Differentiation Involves a Mutual Regulatory Circuit of the Nanog, OCT4, and SOX2 Pluripotency Transcription Factors With Polycomb Repressive Complexes and Stem Cell microRNAs
Vasundhra Kashyap,Naira C. Rezende,Kymora B. Scotland,Sebastian Shaffer,Jenny L. Persson,Lorraine J. Gudas,Nigel P. Mongan +6 more
TL;DR: How aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies is described.
Journal ArticleDOI
Human Induced Pluripotent Stem Cells Develop Teratoma More Efficiently and Faster Than Human Embryonic Stem Cells Regardless the Site of Injection
Ivan Gutierrez-Aranda,Verónica Ramos-Mejía,Clara Bueno,Martin Muñoz-Lopez,Pedro J. Real,Angela Macia,Laura Sánchez,Gertrudis Ligero,Jose L. Garcia‐Parez,Pablo Menendez +9 more
TL;DR: The improved teratoma protocol previously developed by Prokhorova et al. was followed and fully characterized undifferentiated hESCs or iPSCs were used in 6- to 8-week-old non obese diabetic/severe combined immune-deficient mice, ensuring a longer lifespan of inoculated mice.
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