https://ir.ymlib.yonsei.ac.kr/handle/22282913/168748 2026-06-28T14:24:37Z 2026-06-28T14:24:37Z Kim, Jinkyeong Lee, Seungjoon Hwang, Eunkyu Jung, Hwajin Lee, Chanhee Choi, Sang-Han Lee, Sooyeon Kim, Seongbin Moon, Heera Kim, Jisoo Lee, Gina Kim, Yong Gyu Shin, Soogeun Kang, Hyojin Kim, Se Jin Gee, Heon Yung Kim, Seong-Gi Lee, Eunee Kim, Eunjoon 신수근 https://ir.ymlib.yonsei.ac.kr/handle/22282913/212501 2026-06-10T06:30:39Z 2026-05-01T00:00:00Z

Title: Homozygous CHD8 mutation intensifies ASD phenotypes and attenuates sex differences Authors: Kim, Jinkyeong; Lee, Seungjoon; Hwang, Eunkyu; Jung, Hwajin; Lee, Chanhee; Choi, Sang-Han; Lee, Sooyeon; Kim, Seongbin; Moon, Heera; Kim, Jisoo; Lee, Gina; Kim, Yong Gyu; Shin, Soogeun; Kang, Hyojin; Kim, Se Jin; Gee, Heon Yung; Kim, Seong-Gi; Lee, Eunee; Kim, Eunjoon; 신수근 Abstract: CHD8 is a chromatin remodeler implicated in autism spectrum disorders (ASD) and multiple neurodevelopmental disorders, yet heterozygous Chd8-mutant mouse lines often exhibit only mild ASD-related phenotypes, leaving its role unclear. Because a complete knockout of Chd8 causes embryonic lethality, we generated viable homozygous Chd8-mutant mice carrying the human CHD8-Asn2373LysfsX2 mutation using a hybrid (C57BL6/J & times; 129/Sv) genetic background. Compared to heterozygous Chd8(+/N2373K) mice, the homozygous Chd8(N2373K/N2373K) mice showed more robust phenotypes, including increased ASD-related behaviors and brain volume, decreased cerebral blood volume/flow, brain rhythms, and synaptic transmission, and ASD-related transcriptomic changes. Notably, while Chd8(+/N2373K) mice on a pure background predominantly displayed behavioral deficits in males, the homozygous mutants in the hybrid background exhibited more pronounced female phenotypes, suggesting the interaction of genetic background and mutation strength. A direct comparison of Chd8(+/N2373K) and Chd8(N2373K/N2373K) mice on the same hybrid background across brain volume, cerebral blood flow, neuronal firing, synaptic transmission, and transcriptome revealed a gene dosage-dependent attenuation of sexual dimorphic phenotypes that varied by developmental stage and brain region. Transcriptomic analyses further implicated pathways related to synaptic function, RNA splicing, and mitochondrial activity in mediating differences in male-female protection and susceptibility. Thus, a homozygous Chd8 mutation not only intensifies ASD-related traits but can also diminish typical sex-specific severity patterns, uncovering a novel link between mutation strength and sexual dimorphism in ASD.

2026-05-01T00:00:00Z Lee, Dae Gyun Choi, Jun Hyeok Gwak, Seong Jin Cao, Thuy Nguyen Giang Tram, Le Thi Hong Rhee, Won Jong Kim, Byoung Choul Shim, Min Suk https://ir.ymlib.yonsei.ac.kr/handle/22282913/211915 2026-04-28T03:09:38Z 2026-04-01T00:00:00Z

Title: Glutathione-responsive milk-derived exosomes for safe and efficient sonodynamic cancer therapy Authors: Lee, Dae Gyun; Choi, Jun Hyeok; Gwak, Seong Jin; Cao, Thuy Nguyen Giang; Tram, Le Thi Hong; Rhee, Won Jong; Kim, Byoung Choul; Shim, Min Suk Abstract: The encapsulation of sonosensitizers in exosomes has emerged as a potent strategy to enhance the therapeutic outcomes of sonodynamic therapy (SDT). Recently, milk-derived exosome (MExo) has gained significant attention as a scalable and cost-effective alternative to conventional exosomes derived from cell cultures. In this study, glutathione (GSH)-responsive MExos were developed to facilitate the efficient intracellular delivery of sonosensitizers (chlorin e6, Ce6) into human breast cancer cells by leveraging their elevated GSH concentrations. GSH-cleavable diselenide bond-bearing fatty amine derivative (DSe) was incorporated into MExos to achieve GSH-responsive drug release in cancer cells. DSe-incorporated MExo (DMExo) facilitated the release of Ce6 in the reductive cytoplasm. This led to enhanced generation of reactive oxygen species after ultrasound (US) treatment. As a result, Ce6-loaded DMExo triggered significant cell death in MCF-7 human breast cancer cells upon US exposure. These results demonstrate that bioreducible MExo is a safe and effective carrier for efficient SDT against cancer cells.

2026-04-01T00:00:00Z Bae, Geon Hue Kwon, Seong Gyu Choi, Jeong-Woo Hong, Joo Hee Jeon, CheolMin Cho, Areum Shin, Jaeeun Jun, Mee Sook Han, Man-Hoon Choi, Seock Hwan Oh, Ji Won https://ir.ymlib.yonsei.ac.kr/handle/22282913/211955 2026-04-29T08:04:20Z 2026-04-01T00:00:00Z

Title: Comparison between genomic alterations in mouse, pig, and human through whole-genome sequencing Authors: Bae, Geon Hue; Kwon, Seong Gyu; Choi, Jeong-Woo; Hong, Joo Hee; Jeon, CheolMin; Cho, Areum; Shin, Jaeeun; Jun, Mee Sook; Han, Man-Hoon; Choi, Seock Hwan; Oh, Ji Won Abstract: Somatic mutations gradually accumulate as an organism develops and grows. These somatic mutations are not only associated with disease but also serve as important indicators: at the cellular level, they reveal the internal and external effects cells have undergone; at the organism level, they can reveal species-specific patterns. In this study, we conducted whole-genome sequencing on single-cell clonal expansion samples from various tissues of mice, pigs, and human cadavers. A total of 69 samples were analyzed, including muscle, skin, kidney, and other tissues. We compared the number of single nucleotide variants and structural variants across species and tissues, observing differences in the distribution and characteristics of these mutations between humans, mice, and pigs. Additionally, we performed mutational signature analysis to explore the genomic landscapes of these organisms. UV radiation-related mutational signatures were identified in human skin but not in muscle or other animal samples. Furthermore, two mutational signatures, catalogue of somatic mutations in cancer (COSMIC) single base substitution 5 and 40, were mostly present in mice and pigs, although their relative contributions differed. Through these results, we present several hypotheses for estimating species and tissue similarity using Ti/Tv (transition/transversion) ratio, diversity in the number of mutations in the same tissue origin, and the number of single-nucleotide variants is not proportional to that of structural variations. These comparative analyses of genomic alterations across species enhance our understanding of the mechanisms driving somatic mutation accumulation, offering valuable insights into the shared patterns of genomic alterations across species and their implication for animal disease models.

2026-04-01T00:00:00Z Sun, Chunjiao Zhao, Jingshuang Li, Nana Yao, Xuebo Wang, Yanfei Kim, Chul Hoon Bok, Jinwoong Peng, Anthony W. Xu, Zhigang https://ir.ymlib.yonsei.ac.kr/handle/22282913/212515 2026-06-10T07:04:05Z 2026-04-01T00:00:00Z

Title: Alternative splicing of the Rbm24 gene is essential for cochlear hair cell stereocilia integrity and hearing function in mice Authors: Sun, Chunjiao; Zhao, Jingshuang; Li, Nana; Yao, Xuebo; Wang, Yanfei; Kim, Chul Hoon; Bok, Jinwoong; Peng, Anthony W.; Xu, Zhigang Abstract: Cochlear hair cells are the mechanosensitive receptor cells responsible for detecting sound information. They are characterized by their apical F-actin-filled stereocilia that are essential for mechano-electrical transduction. Previously, we and other groups reported that RNA Binding Motif Protein 24 (RBM24) plays pivotal roles in stereo-cilia development and maintenance by regulating pre-mRNA alternative splicing and mRNA stability. In the present work, we show that exon 4 of the mouse Rbm24 gene is subjected to alternative splicing. Inclusion of exon 4 in Rbm24 mRNA results in premature translational stop, giving rise to a short isoform of RBM24 (RBM24-S). Notably, while sharing the same RNA-recognition motif, the canonical RBM24 long isoform (RBM24-L) and RBM24-S can bind different mRNA targets to affect their splicing and/or stability. Deletion of Rbm24 exon 4 in mice abolishes the expression of Rbm24(+e4) transcripts that encode for RBM24-S, and both homozygote and heterozygote mice suffer from severe hearing loss. Further investigations revealed that Rbm24 exon 4 deletion leads to stereocilia disorganization and eventually hair cell loss. Moreover, overexpression of RBM24-L in the hair cells leads to significant stereocilia deficits as well as profound hearing loss. Finally, we identified several RBM24 targets such as Strc, whose dysregulation contributes to stereocilia disorganization as well as hearing loss in Rbm24 deficient mice. Taken together, our present data suggest that Rbm24 is subjected to alternative splicing and appropriate RBM24 expression levels are important for stereocilia integrity and hearing function.

2026-04-01T00:00:00Z