Acceleration of somatic cell reprogramming into the induced pluripotent stem cell using a mycosporine-like amino acid, Porphyra 334

Junsang Yoo,Hyein Kim,Hoon Ryu,Sung Joo Jang,Seung Jae Hyeon,Jongpil Kim,Jeong Hun Lee,Sang Hyun Moh,Junyeop Kim,Hyo Hyun Seo,Seung Taek Oh

doi:10.1038/s41598-020-60680-5

Abstract

Porphyra 334 (P334), a mycosporine-like amino acid (MAA), is a secondary metabolite found in diverse marine and terrestrial organisms and has several beneficial effects on fibroblast proliferation, wound healing, and antioxidant activity. Here, we report that P334 accelerates the cell reprogramming process of mouse tail-tip fibroblasts (TTFs) and human dermal papilla (HDP) cells into induced pluripotent stem cells (iPSCs). We found that P334 significantly improved the cell reprogramming efficiency by activating the tri-methylation of histone 3 lysine 4 (H3K4me3), which controls mesenchymal to epithelial transition (MET) during the reprogramming process. Thus, we found that P334 directly regulates epigenetic changes, providing an efficient approach for natural compound-based cell reprogramming.

Highlights

Cell reprogramming into pluripotency involves the generation of embryonic stem cell (ESC)-like cells from somatic cells via the ectopic expression of defined transcriptional factors[16,17]
We observed a typical spectrum with prominent spectral peaks with a retention time of 7.04 min for Porphyra 334 (P334), confirming that it was present in the mixture of purified mycosporine-like amino acid (MAA) (Fig. 1B)
We determined that mesenchymal to epithelial transition (MET) mediates P334-induced epigenetic changes during cell reprogramming (Fig. 6)

Summary

Introduction

Cell reprogramming into pluripotency involves the generation of embryonic stem cell (ESC)-like cells from somatic cells via the ectopic expression of defined transcriptional factors[16,17]. Yamanaka demonstrated that the ectopic expression of four transcription factors (Oct[4], Klf[4], Sox[2], and c-Myc (OSKM)) could induce the conversion of murine somatic cells to induced pluripotent stem cells (iPSCs)[18]. Studies using iPSCs provide a unique experimental approach to investigate key questions regarding cell fate conversion and epigenetic changes following the induction of pluripotency marker genes and the suppression of somatic cell genetic characteristics. Cell-to-cell and cell-to-matrix interactions are involved in the EMT process and lead to the loss of epithelial characteristics and the acquisition of mesenchymal lineage markers by downregulating E-cadherin (Cdh1) and upregulating Snail and Slug. Our finding supports a model in which the natural compound P334 affects the epigenetic state associated with cell fate conversion, which has important implications for the application of P334 in stem cell biology research and regenerative medicine

Methods

Results

Conclusion