GENOMIC AND EPIGENETIC MODIFICATIONSCONTROLLING STEM CELL DIFFERENTIATION ANDREGENERATIVE POTENTIAL IN EARLY DEVELOPMENT:A COMPREHENSIVE CRITICAL REVIEW

Abstract

The precise control of stem cell differentiation and regenerative capacity during early development is governed by an intricate interplay of genomic and epigenetic regulatory mechanisms. Disruptions within these pathways are now recognised as fundamental drivers of oncogenic transformation, tumour heterogeneity, and therapy resistance across multiple cancer types. Understanding these regulatory axes is therefore essential to advancing both developmental biology and translational oncology.

Objective: This review critically appraises the current body of literature regarding the genomic and epigenetic modifications—including DNA methylation, histone modifications, chromatin remodelling, non-coding RNA networks, and three-dimensional genome organisation—that govern stem cell self-renewal, lineage commitment, and regenerative potential during early development, with specific emphasis on how their aberration contributes to cancer initiation and progression.

Methods: A systematic search of PubMed, Web of Science, Scopus, and Google Scholar databases was conducted, encompassing articles published between 2018 and 2026. Studies were selected based on relevance to epigenetic regulation of stem cells, developmental biology, and cancer pathogenesis. Both primary research articles and high-quality review papers were critically evaluated and synthesised.