Generating pluripotent stem cells: Differential epigenetic changes during cellular reprogramming

Abstract

Pluripotent stem cells hold enomous potential for therapuetic applications in tissue replacement therapy. Reprogramming somatic cells from a patient donor to generate pluripotent stem cells involves both ethical concerns inherent in the use of embryonic and oocyte-derived stem cells, as well as issues of histocompatibility. Among the various pluripotent stem cells, induced pluripotent stem cells (iPSC)—derived by ectopic expression of four reprogramming factors in donor somatic cells—are superior in terms of ethical use, histocompatibility, and derivation method. However, iPSC also show genetic and epigenetic differences that limit their differentiation potential, functionality, safety, and potential clinical utility. Here, we discuss the unique characteristics of iPSC and approaches that are being taken to overcome these limitations.

The Olfactory Neural Epithelium As a Tool in Neuroscience

“…It is known that the reprogramming procedure to produce iPSCs leaves some residual epigenetic markers in the resulting iPSCs genome, which possibly interfere with the investigation of differential gene expression and epigenetic processes in brain disorders [10]. In addition, the procedures involved in generating iPSCs and deriving neurons from these are very time-consuming, costly and are not high-throughput.…”

Re-Epithelialization: A Key Element in Tracheal Tissue Engineering

“…Moreover, iPSCs show genetic and epigenetic changes during reprogramming, especially tumorigenic mutations, which limit their differentiation potential, functionality, safety and potential clinical utility [120,121]. This is because the true replication model of iPSCs in vivo is unknown and the long-term influence of epigenetic changes introduced during iPS derivation and differentiation remains incompletely understood.…”

Epigenetic regulation of stemness maintenance in the neurogenic niches

“…For instance, Oct4 and Nanog promoters are demethylated and histones H3 lysine 4 (K4) and lysine 27 mostly exhibit patterns of trimethylation [101,106,122] . However, reprogramming of NSCs into iPSCs is often incomplete and leaves epigenetic marks including DNA methylation, chromatin modification and transcriptional regulation in the resulting iPSC genome [123,124] known as epigenetic "memory". Partially reprogrammed cell lines are characterized by an absence of complete downregulation of the exogenous reprogramming factors and partial demethylation and reactivation of pluripotency genes [101,104] .…”