The landscape and plasticity of transposable element expression in an adult stem cell of high physiological and clinical significance

Abstract

Abstract Transposable elements (TEs) contribute to diverse aspects of stem cell biology, particularly in germline and pluripotent stem cells, which typically exhibit more open chromatin. In human adult stem cells (ASCs), however, a comprehensive framework describing the landscape and plasticity of TE expression and how these patterns may inform studies of ASC biological properties and considerations relevant to clinical translations has been lacking. Here, using human adipose-derived mesenchymal stem cells (hADSCs) as an adult stem cell paradigm, we combined transcriptomic profiling with integrative bioinformatics to map the TE expression landscape in hADSCs across multiple biologically and manufacturing-relevant contexts. We examined TE expression dynamics across culture conditions, senescence, and donor-related backgrounds, and found that TE expression patterns in hADSCs were highly plastic in response to environmental cues. Comparative analyses of TE and gene expression showed that TE patterns and dynamics correlated with transcriptomic signatures related to mesenchymal stem/stromal cells (MSCs) biological states. HERV16-int, L1MEh, and MER61E emerged as recurrent, context-responsive TE candidates associated with transcriptional signatures related to MSC immune-related, stemness-related, and senescence-related programs. This work addresses a gap in MSC TE expression profiling and provides a framework for prioritizing candidate TE-expression features with potential relevance to future MSC manufacturing and quality-assessment studies, pending orthogonal and functional validation.