Seyed M.A.H. Rad, Abdollah Mohammadi-Sangcheshmeh, Taravat Bamdad, Lida Langroudi, Amir Atashi, Majid Lotfinia, Ehsan Arefian, Eduardo L. Gastal and Masoud Soleimani Pages 300 - 311 ( 12 )
Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) and have the potency to differentiate into three germ layers (ectoderm, endoderm, and mesoderm). This potency of ESCs, called pluripotency, is critical for maintaining stemness. Transcriptional regulatory circuitry preserving stemness consists of transcription factors (TFs), epigenetic mechanisms, microRNAs (miRNAs or miRs), and long non-coding RNAs (lncRNAs). In this circuitry, components assist each other to activate essential genes for maintaining pluripotency and suppressing lineage-specific genes. TFs act directly by binding to their binding sites in the genome or indirectly by activating another gene (such as a miR), epigenetic mechanisms play their role by providing an activatory or inhibitory context for transcription, miRNAs regulate gene expression at the post-transcriptional level, and lncRNAs act as a scaffold function for epigenetic elements, regulating gene expression in ESCs. All these factors create a crossroad and collaborate to sustain stemness in the ESCs. Herein, we explain the role of each member in this circuitry and demonstrate the significance of the crossroad for keeping stemness.
ESCs, pluripotency, self-renewal, core transcriptional regulatory circuitry.
Stem Cell Technology Research Center, Tehran, Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Pakdasht, Tehran, Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Stem Cell and Tissue Engineering Research Center, Shahroud University of Medical Science, Shahroud, Department of Biochemistry, Pasteur Institute of Iran, Tehran, Department of Microbiology, School of Biology, College of Science, University of Tehran, Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, lllinois, Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran