Understanding Embryonic Stem Cell Pluripotency Through Its Key Players

R. Govindan
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Abstract

Certain transcription factors, cofactors, chromatin regulators are identified as the key players in establishing the embryonic stem cell ground state. The activation and silencing of genes in response to potency and lineage development act as the regulatory circuits. Insights into these regulatory circuitory have uncovered fundamental genetic and epigenetic mechanisms that control gene expressions to maintain the ground state. At one end of the circuit are the core transcription factors that self regulate their own gene expression. These factors further activate transcription of genes involved in pluripotency and contribute to the arrest of expression of lineage specific genes. The core transcription factors mediate binding of the enhancers with signaling factors there by extending the circuit to communicate the signals directly to the genes regulated by the core factors. The core factors also create an undifferentiated state through chromatin regulators that remodify the regulatory gene sequences of specific lineages to inactive states. Understanding the embryonic stem cell ground state in terms of its various regulatory aspects serves as both a baseline for understanding the changes that occur as cells differentiate and develop and as a means to understand the basic biology of these cells. It also helps in understanding the mechanisms behind induced pluripotent cells in vitro culture conditions that might contribute to stem cell based translational medicines.
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通过关键参与者了解胚胎干细胞多能性
某些转录因子、辅助因子、染色质调节因子在胚胎干细胞基态的建立中起着关键作用。基因的激活和沉默响应效力和谱系发育作为调控回路。对这些调控回路的深入了解揭示了控制基因表达以维持基态的基本遗传和表观遗传机制。在回路的一端是自我调节自身基因表达的核心转录因子。这些因子进一步激活参与多能性的基因转录,并有助于抑制谱系特异性基因的表达。核心转录因子介导增强子与信号因子的结合,将信号直接传递给受核心转录因子调控的基因。核心因子还通过染色质调节因子将特定谱系的调节基因序列重新修饰为非活性状态,从而产生未分化状态。了解胚胎干细胞基态的各种调控方面,既是理解细胞分化和发育过程中发生的变化的基础,也是理解这些细胞基本生物学的一种手段。它也有助于理解在体外培养条件下诱导多能细胞的机制,这可能有助于基于干细胞的转化药物。
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