Transcriptomic profiling of endometrial and dermal mesenchymal stromal cells before and after treatment with menstrual fluid

Introduction: Human endometrium is one of the unique organs, capable of scarless regeneration after injury during menstrual cycle. However, it is disputable whether this feature should be attributed to specific regulatory molecules present in the wound environment (menstrual fluid) or to the tissue-specific properties of endometrial mesenchymal stromal cells (eMSC), which are the main participants of wound healing. We aim to elucidate the role of eMSC tissue-specificity in wound healing. Methods: We compared eMSC and dMSC transcriptomic profiles in response to MF with those of stromal cells from scar-forming organs - dermal MSC. Results: We have found that menstrual fluid induces a profound inflammatory response in both eMSC and dMSC, but a tissue-specific component was present in the transcriptomic changes. Furthermore, transcriptomic tissue-specificity is present as after MF treatment as before it, and was validated by in vivo single-cell RNA-sequencing data from Human Protein Atlas. This tissue-specificity is related to embryonic development and morphogenesis, suggesting the role of “developmental imprinting” in its establishment. Finally, we refined transcription factors from stably tissue-specific genes that may explain the unique properties of eMSC and endometrium itself and may serve as the potential targets to induce regeneration in scar-forming organs. Conclusion: eMSC possess tissue-specific properties, including stable expression of transcription factors that may explain the scarless regeneration of endometrium.