차혁진 (서울대학교 약학대학)

한빛사논문

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서울대학교 약학대학

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Sci. Adv., Nov 24 2023, 9 (47) | https://doi.org/10.1126/sciadv.adi8454 Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction

Jumee Kim^1†, Somi Kim ^2†, Seung-Yeon Lee ^1†, Beom-Ki Jo ¹, Ji-Young Oh ¹, Eun-Ji Kwon ¹, Keun-Tae Kim ¹, Anish Ashok Adpaikar ³, Eun-Jung Kim ³, Han-Sung Jung ³, Hwa-Ryeon Kim ⁴, Jae-Seok Roe ⁴, Chang Pyo Hong ⁵, Jong Kyoung Kim ^2*, Bon-Kyoung Koo ^6,7*, Hyuk-Jin Cha ^1*

¹College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

²Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.

³Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea.

⁴Department of Biochemistry, Yonsei University, Seoul, Korea.

⁵Theragen Bio Co., Ltd, Seongnam 13488, Republic of Korea.

⁶Center for Genome Engineering, Institute for Basic Science, 55, Expo-ro, Yuseong-gu, Daejeon 34126, Republic of Korea.

⁷Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, Vienna 1030, Austria.

^†These authors contributed equally to this work.

^*Corresponding author: H.-J.C.; B.-K.K.; J.K.K.

Abstract

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-27)
연구진국내(교신)+국외 연구진
분야 의약학 > 재생의학

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