한빛사
>
한빛사논문
한빛사논문
- 조회454
Sci. Adv., Mar 28 2025, 11 (13) | https://doi.org/10.1126/sciadv.adp8271
Perturbed cell fate decision by schizophrenia-associated AS3MTd2d3 isoform during corticogenesis
Seunghyun Kim 1 †, Youngsik Woo 1 †, Dahun Um 1 †, Inseop Chun 1 †, Su-Jin Noh 1 †, Hyeon Ah Ji 1, Namyoung Jung 1, Bon Seong Goo 1, Jin Yeong Yoo 1, Dong Jin Mun 1, Tran Diem Nghi 1, Truong Thi My Nhung 1, Seung Hyeon Han 1, Su Been Lee 1, Wonhyeok Lee 1, Jonghyeok Yun 1, Ki Hurn So 1, Dae-Kyum Kim 2 3, Hyunsoo Jang 4, Yeongjun Suh 1, Jong-Cheol Rah 5, Seung Tae Baek 1 6, Ki-Jun Yoon 4, Min-Sung Kim 1 6 *, Tae-Kyung Kim 1 6 *, Sang Ki Park 1 6 *
1Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
2Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec H3G 1A4, Canada.
3Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
4Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
5Korea Brain Research Institute, Daegu 41062, Republic of Korea.
6Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul 03772, Republic of Korea.
1Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
2Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec H3G 1A4, Canada.
3Cancer Research Program, Research Institute of McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
4Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
5Korea Brain Research Institute, Daegu 41062, Republic of Korea.
6Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul 03772, Republic of Korea.
†These authors contributed equally
*Corresponding authors: correspondence to Min-Sung Kim, Tae-Kyung Kim or Sang Ki Park
Abstract
The neurodevelopmental theory of schizophrenia emphasizes early brain development in its etiology. Genome-wide association studies have linked schizophrenia to genetic variations of AS3MT (arsenite methyltransferase) gene, particularly the increased expression of AS3MTd2d3 isoform. To investigate the biological basis of this association with schizophrenia pathophysiology, we established a transgenic mouse model (AS3MTd2d3-Tg) ectopically expressing AS3MTd2d3 at the cortical neural stem cells. AS3MTd2d3-Tg mice exhibited enlarged ventricles and deficits in sensorimotor gating and sociability. Single-cell and single-nucleus RNA sequencing analyses of AS3MTd2d3-Tg brains revealed cell fate imbalances and altered excitatory neuron composition. AS3MTd2d3 localized to centrosome, disrupting mitotic spindle orientation and differentiation in developing neocortex and organoids, in part through NPM1 (Nucleophosmin 1). The structural analysis identified that hydrophobic residues exposed in AS3MTd2d3 are critical for its pathogenic function. Therefore, our findings may help to explain the early pathological features of schizophrenia.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-31)
- 국내 연구진
- 생명과학 > 신경생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 논문보기
