This study investigated the molecular mechanisms of stem cell pluripotency in Nigerian populations, addressing a critical knowledge gap in understanding population-specific variations in stem cell biology. Using comprehensive molecular analyses including transcriptomics, epigenomics, and functional characterisation, we examined induced pluripotent stem cells (iPSCs) derived from diverse Nigerian ethnic groups.While core pluripotency transcription factors (OCT4, SOX2, NANOG) showed strong conservation, Nigerian-derived iPSCs exhibited distinctive molecular features. Specifically, these cells demonstrated altered isoform usage, population-specific expression patterns in extended pluripotency networks, and unique epigenetic landscapes.Signalling pathway analysis revealed enhanced WNT/β-catenin activity, heightened JAK/STAT sensitivity, and reduced FGF/ERK signalling compared to reference lines. Novel regulatory elements were identified, including population-specific enhancers, long non-coding RNAs, alternative promoters, and chromatin interaction hubs.Functional characterisation demonstrated that Nigerian-derived iPSCs possess enhanced stress resistance and distinctive differentiation propensities, with significantly higher efficiency in hematopoietic lineage specification. The cells demonstrated approximately 30% better viability under challenging conditions and a 25% improvement in hematopoietic progenitor generation compared to the reference lines.Comparative analysis positioned Nigerian-derived iPSCs as molecularly distinct from European and East Asian lines while sharing features with other African-derived cells. These findings challenge the concept of a universal pluripotent state, supporting a model of population-specific implementations of pluripotency that achieve similar functional outcomes through different molecular configurations
