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울산대학교 의과대학, 서울아산병원

Nat. Commun., Feb 19 2024, 15 (1) | https://doi.org/10.1038/s41467-024-45647-8 PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development

Jong Geol Lee^1,2,19,20, Jung-Min Yon^1,3,20, Globinna Kim^1,3, Seul-Gi Lee⁴, C-Yoon Kim⁵, Seung-A Cheong¹, Hyun-Yi Kim⁶, Jiyoung Yu¹, Kyunggon Kim^1,7,Young Hoon Sung^1,3, Hyun Ju Yoo^1,7, Dong-Cheol Woo^1,8, Jin Kyung Rho^1,9, Chang Hoon Ha^1,9, Chan-Gi Pack^1,8, Seak Hee Oh¹⁰, Joon Seo Lim¹, Yu Mi Han¹¹, Eui-Ju Hong¹², Je Kyung Seong^2,13, Han-Woong Lee¹⁴, Sang-Wook Lee^2,15, Ki-Up Lee^1,9, Chong Jai Kim^1,16, Sang-Yoon Nam¹⁷, You Sook Cho^1,18 & In-Jeoung Baek^1,2,3

¹Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.

²Korea Mouse Phenotyping Center (KMPC), Seoul 08826, Korea.

³Department of Cell and Genetic Engineering, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

⁴Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 05029, Korea.

⁵College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.

⁶NGeneS Inc, Ansan 15495, Korea.

⁷Department of Digital Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

⁸Department of Biomedical Engineering, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

⁹Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

¹⁰Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

¹¹Research Institute of Medical Science, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

¹²College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea.

¹³College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

¹⁴Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.

¹⁵Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

¹⁶Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

¹⁷College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.

¹⁸Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

¹⁹Present address: Biological Resources Research Group, Bioenvironmental Science & Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology (KIT), Jinju 52834, Korea.

²⁰These authors contributed equally: Jong Geol Lee, Jung-Min Yon.

Correspondence and requests for materials should be addressed to You Sook Cho or In-Jeoung Baek.

Abstract

Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-21)
연구진국내 연구진
분야 의약학 > 응용의학

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