Epigenetic setting and reprogramming for neural cell fate determination and differentiation

Abstract

In the mammalian brain, epigenetic mechanisms are clearly involved in the regulation of self-renewal of neural stem cells and the derivation of their descendants, i.e. neurons, astrocytes and oligodendrocytes, according to the developmental timing and the microenvironment, the 'niche'. Interestingly, local epigenetic changes occur, concomitantly with genome-wide level changes, at a set of gene promoter regions for either down-or upregulation of the gene. In addition, intergenic regions also sensitize the availability of epigenetic modifiers, which affects gene expression through a relatively long-range chromatinic interaction with the transcription regulatory machineries including non-coding RNA (ncRNA) such as promoter-associated ncRNA and enhancer ncRNA. We show that such an epigenetic landscape in a neural cell is statically but flexibly formed together with a variable combination of generally and locally acting nuclear molecules including master transcription factors and cell-cycle regulators. We also discuss the possibility that revealing the epigenetic regulation by the local DNA -RNA -protein assemblies would promote methodological innovations, e.g. neural cell reprogramming, engineering and transplantation, to manipulate neuronal and glial cell fates for the purpose of medical use of these cells.

Dissecting the transcriptional regulatory networks of promoter-associated noncoding RNAs in development and cancer

“…In addition, it has been proposed that pancRNAs might bind epigenetic factors, promoting the fold of the chromatin into a transcriptionally competent ternary structure, named R-Loop and composed by the nascent RNA annealed with its complementary ssDNA and the nontemplate ssDNA. Another possibility was that pancRNAs may perhaps stabilize the active state of chromatin through the association with small dsRNAs, which in turn, could cover the catalytic site of methyl transferases [38].…”

Nature or Nurture – Will Epigenomics Solve the Dilemma?

“…There is a growing body of evidence of the importance of epigenetic regulation in behavioral and cognitive processes [71]. Epigenetic influence has been observed in brain development and neuroplasticity [2,49,50,154,163,173], neuron differentiation [86], also learning and memory formation [24,28,37,51,54,90,144], including fear memory formation [77,89,131]. Epigenetic mechanisms are also involved in aging, neurological diseases, mood and psychotic disorders, cognitive impairments or response to trauma [19,50,83,144,163,169,173].…”

Study of the chlorpyrifos neurotoxicity using neural differentiation of adipose tissue‐derived stem cells

“…Nestin is a neural stem/progenitor cell marker (Michalczyk and Ziman, 2005). NeuN is a specific marker of postmitotic neurons (Lavezzi et al, 2013), and NEFL is abundantly found in mature neurons (Imamura et al, 2014). Synaptophysin is an integral membrane protein of small synaptic vesicles, which is present in mature terminals and outgrowing axons (Bergmann et al, 1991(Bergmann et al, , 1993Grabs et al, 1994).…”