Stem Cells Have Different Needs for REST

Abstract

Embryonic stem cells (ESCs) are believed to possess the innate capacity to differentiate into any of the multitude of cell types that make up the body, a capacity known as pluripotency (http://en.wikipedia.org/wiki/Pluripotent). For a cell to differentiate and adopt the identity of a specific cell lineage, transcriptional mechanisms must “switch on” a suite of genes that encode proteins characteristic of that cell type. Simultaneously, other genes characteristic for other cell types must reliably be “switched off.” As the proper regulation of gene expression is essential for cellular differentiation and normal development, understanding how differentiation programs regulate the correct number and types of cells in a developing organism is a fundamental issue in biology and medicine. Differentiation programs employ regulatory factors that both promote and repress transcription. For example, certain vertebrate activating transcription factors (http://en.wikipedia.org/wiki/Transcription_(genetics)), including Mash1 (Mammalian achaete scute-like 1), Math1 (Mouse atonal homologue 1), and the Neurogenin family [1], have been shown to be sufficient and/or required to promote differentiation into a neuronal cell type, while transcriptional repressors have been shown to play a key role in determining pluripotency and differentiation [2]. The Notch family of membrane receptors exerts strong inhibition of differentiation into neurons by increasing the cellular levels of powerful transcriptional repressors, such as the nuclear factors Hes1–5. Most factors of this family function as repressors of neurogenesis (http://en.wikipedia.org/wiki/Neurogenesis) by directly binding to the promoter of neurogenic genes such as Mash1, repressing the gene [3].