Title:Pluripotency Crossroads: Junction of Transcription Factors, Epigenetic Mechanisms, MicroRNAs, and Long Non-coding RNAs
Volume: 12
Issue: 4
Author(s): Seyed M.A.H. Rad, Abdollah Mohammadi-Sangcheshmeh, Taravat Bamdad, Lida Langroudi, Amir Atashi, Majid Lotfinia, Ehsan Arefian, Eduardo L. Gastal and Masoud Soleimani
Affiliation:
Keywords:
ESCs, pluripotency, self-renewal, core transcriptional regulatory circuitry.
Abstract: 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.