HERVs and Epigenetic Regulators Transcriptional Expression After Chondrogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells

TL;DR

This study explores how certain retroviruses and their regulators change during the transformation of fat-derived stem cells into cartilage cells.

Contribution

The study reveals family-specific interactions between HERVs, epigenetic regulators, and pluripotency markers during chondrogenesis.

Findings

HERV-K and HERV-W showed a trend toward decreased expression during chondrogenic differentiation.

TRIM28 expression was significantly reduced, while SETDB1 showed a decreasing trend.

HERV-W expression correlated negatively with TRIM28 and positively with SETDB1 in differentiated cells.

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into various connective tissue cell types. Adipose tissue provides a rich source of MSCs (ADSCs), which can differentiate into osteoblasts, adipocytes, and chondroblasts. Pluripotency factors such as SOX2, NANOG, and OCT4 maintain MSC stemness, whereas human endogenous retroviruses (HERVs) and their epigenetic regulators TRIM28 and SETDB1 have been implicated in transcriptional regulation and cell fate decisions. This study investigated the transcriptional expression of HERV-H, -K, and -W, TRIM28, SETDB1, and pluripotency markers (NANOG, OCT4, SOX2) during chondrogenic differentiation of ADSCs using Real-Time PCR. Chondrogenesis was confirmed by aggrecan (ACAN) upregulation and aggrecan immunostaining. Although no statistically significant differences were observed for HERV-H, HERV-K, or HERV-W, HERV-K and HERV-W showed a trend toward decreased expression in differentiated cells, consistent with the overall shift in transcriptional profile during lineage commitment. TRIM28 expression was significantly reduced, while SETDB1 showed a decreasing trend. Among pluripotency markers, OCT4 was significantly downregulated, whereas NANOG and SOX2 remained stable. Correlation analyses revealed that in differentiated ADSCs, HERV-W expression correlated negatively with TRIM28 and positively with SETDB1, while no correlations were found for HERV-H or HERV-K. These findings suggest that specific HERV families and their epigenetic regulators may undergo coordinated modulation during chondrogenic differentiation, supporting a complex and family-specific interplay between retroelement regulation, pluripotency factors, and MSC lineage commitment.

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