Cell-free culture conditioned medium elicits pancreatic β cell lineage-specific epigenetic reprogramming in mice

Koichi Kawamoto, Tomofumi Ohashi, Masamitsu Konno, Naohiro Nishida, Jun Koseki, Hidetoshi Matsui, Daisuke Sakai, Toshihiro Kudo, Hidetoshi Eguchi, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


There are several obstacles to overcome prior to achieving cellular reprogramming of pancreatic β cells in vitro and in vivo. The present study demonstrated that the transfer of epigenetic phenotypes was achieved in the cell-free conditioned medium (CM) of pancreatic insulinoma MIN6 cell cultures. The comparison of a subpopulation of MIN6, m14 and m9 cells indicated that MIN6-m14 cells were more prone to cellular reprogramming. Epigenetic profiling revealed that the transcription factor pancreas/duodenum homeobox protein 1 (Pdx1) was differentially associated among the clones. The culture of differentiated adipocytes in the CM of MIN6-m14 cells resulted in the induction of insulin mRNA expression, and was accompanied by epigenetic events of Pdx1 binding. The epigenetic profiling indicated that Pdx1 is preferentially associated with a previously uncharacterized region of the endoplasmic reticulum (ER) disulfide oxidase, ER oxidoreductin 1 gene. Therefore, the results of the present study indicated that the CM of MIN6 cells was able to induce a pancreatic β cell-like phenotype in differentiated adipocytes. These data provide additional support for the utility of cell-free CM for cellular reprogramming.

Original languageEnglish
Pages (from-to)3255-3259
Number of pages5
JournalOncology Letters
Issue number3
Publication statusPublished - Sep 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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