Role of epigenetics in cellular reprogramming; from iPSCs to disease modeling and cell therapy

Abstract

Epigenetics play a fundamental role in induced pluripotent stem cell (iPSC) technology due to their effect on iPSC's reprogramming efficiency and their subsequent role in iPSC differentiation toward a specific lineage. Epigenetics can skew the differentiation course of iPSCs toward a specific lineage based on the epigenetic memory of the source cells, or even lead to acquisition of new cell phenotypes, due to its aberrations during reprogramming. This viewpoint discusses key features of the epigenetic process during iPSC reprogramming/differentiation and outlines important epigenetic factors that need to be considered for successful generation and differentiation of iPSCs for downstream applications.

Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells

“…The culturing of stem cells in a dish itself possesses a stochasticity that contributes to inconsistent differentiation in even carefully controlled environments 94 . Variable differentiation potential may be attributed to the process of reprogramming as well as the introduction of both genetic and epigenetic changes during culture, which are currently poorly understood 95 – 97 . Additional sources of variation include the mode of culture, cell line differences, and a vast repository of matrices, small molecules, and techniques, many of which may be proprietary or susceptible to batch variability.…”

Vascular organoids: unveiling advantages, applications, challenges, and disease modelling strategies

“…iPSCs derived from donors with shorter telomeres might manifest aging-associated features due to telomere shortening during cell division. Importantly, while telomere length is one aspect of cellular aging, iPSCs derived from older donors with shorter telomeres may also exhibit other age-related epigenetic changes and functional shifts [ 54 , 55 ].…”

“…Additionally, research have revealed that blood vessels possess a memory of their cellular origins. The identity of vascular cells within a vessel is not solely determined by signals from the surrounding tissue but also by the identity of their parental cells, known as cells of origin [ 55 , 101 – 105 ]. Therefore, the tissue source of cells used to generate iPSC lines also plays a role, as residual epigenetic memory can influence the phenotype of iPSCs and bias their differentiation towards a specific lineage [ 55 , 104 , 106 ].…”

“…The identity of vascular cells within a vessel is not solely determined by signals from the surrounding tissue but also by the identity of their parental cells, known as cells of origin [ 55 , 101 – 105 ]. Therefore, the tissue source of cells used to generate iPSC lines also plays a role, as residual epigenetic memory can influence the phenotype of iPSCs and bias their differentiation towards a specific lineage [ 55 , 104 , 106 ]. Human iPSCs have been derived from various cell sources, including fibroblasts [ 7 ], keratinocytes, and mononuclear cells from healthy individuals or patients [ 22 , 107 , 108 ].…”

Application of patient-derived induced pluripotent stem cells and organoids in inherited retinal diseases

“…Reprogramming technology is considered one of the most important advances in the field of stem cell research and regenerative medicine [ 14 , 19 , 20 ]. Fibroblasts were the first somatic cells to be applied for reprogramming into human and mouse iPSCs [ 21 , 22 ].…”