https://scholar.dgist.ac.kr/handle/20.500.11750/6121 2026-04-04T17:14:47Z https://scholar.dgist.ac.kr/handle/20.500.11750/60112 Title: Sensory abnormalities in autism spectrum disorder and their in vitro modeling Author(s): Kim, Taeyeon; Lee, Juwon; Lee, Jiye; Jo, Hyeokjin; Oh, Yohan; Kim, Yong Jun; Seo, Jinsoo Abstract: Autism Spectrum Disorder (ASD) is characterized by deficits in social interaction, alongside abnormal sensory reactivity that often manifests as avoidance or repetitive behaviors. This review proposes that these core features may stem from somatosensory system dysfunction responsible for processing sensory information driven by an underlying excitatory-inhibitory (E/I) imbalance, a common finding in ASD models, which could drive such sensory impairments and ultimately contribute to the core social and behavioral deficits. We explore how recent advancements in hiPSC-derived assembloid models, which integrate multiple components of the human somatosensory pathway, provide a powerful platform to investigate these mechanisms. Crucially, this review not only highlights the promise of these models but also provides a critical evaluation of their inherent limitations, including cellular immaturity and the absence of key non-neuronal components. By examining the ongoing strategies to overcome these challenges, such as advanced co-culture systems, xenotransplantation, and bioengineering, this review offers a comprehensive outlook on the future of assembloid technology in elucidating ASD pathophysiology and developing novel therapeutic strategies. 2025-10-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60111 Title: Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species Author(s): Lee, Jongsun; Lee, Bora; Lee, Hyein; Kim, Eun Ji E.; Kim, Sieun S.; Kwon, Hyunwoo C.; Lee, Hanseul; Lee, Gee - Yoon; Hong, Woojin; Ham, Seokjin; Yang, Jae Won; Park, Heeju; Moreno, Tatiana M.; Brown, Michelle E.; Park, Hae- Eun H.; Kim, Eunah; Jung, Yoonji; Kang, Eunseok; Park, Sangsoon; Shin, Yeo Jin; Ha, Seokjun G.; Kwon, Sujeong; Hwang, Seungjae; Min, Hyemin; Kumsta, Caroline; Lim, Chunghun; Kang, Chanhee; Seo, Jinsoo; Lee, Kwang-Pyo; Leea, Seung-Jae, V Abstract: Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on aging remains elusive. Here, we show that Pelota, the ribosome rescue factor, promotes longevity and protects against age-related pathological phenotypes in multiple metazoan species. By performing a targeted genetic screen, we find that Pelota is indispensable for longevity in the nematode Caenorhabditis elegans. We show that Pelota mitigates premature senescence in cultured human cells, muscle aging in mice, and neuropathology in cellular and organoid models ofAlzheimer's disease. Mechanistically, we demonstrate that Pelota maintains autophagy-mediated proteostasis, by preventing the hyperactivation of mechanistic target of rapamycin signaling. Overall, our work highlights the conserved functional significance of RQC, regulated by Pelota, in extending lifespan and protecting diverse species against age-associated disease phenotypes. 2025-07-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60109 Title: Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids Author(s): Chun, Min Young; Jung, Sang-Hyuk; Choe, Juran; Lee, Seung-yeon; Kim, Hang-Rai; Son, Hyo Jin; Choi, Yejoo; Cho, Minyoung; Kim, Beomsu; Jang, Hyemin; Choi, Seong Hye; Jeong, Jee Hyang; Son, Sang Joon; Hong, Chang Hyung; Roh, Hyun Woong; Na, Duk L.; Seo, Sang Won; Won, Hong-Hee; Seo, Jinsoo; Kim, Hee Jin Abstract: INTRODUCTION Polygenic risk score (PRS) identifies individuals at high genetic risk for Alzheimer's disease (AD), but its utility in predicting cognitive trajectories and AD pathologies remains unclear. We optimized PRS (optPRS) for AD, investigated its association with cognitive trajectories and AD phenotypes of cerebral organoids. METHODS Using genome-wide association study (GWAS) summary statistics from a European population, we developed optPRS to predict AD in Korean individuals (n = 1634). We analyzed the association between optPRS and cognitive trajectories (n = 771). We generated induced pluripotent stem cell-derived cerebral organoids from patients with high (n = 3) and low (n = 4) optPRS to evaluate amyloid beta (A beta) and phosphorylated tau (p-tau) levels. RESULTS OptPRS predicted AD dementia and A beta positivity, independent of apolipoprotein E (APOE). Higher optPRSs correlated with rapid cognitive decline. Cerebral organoids from the high optPRS group exhibited increased A beta insolubility and p-tau levels. CONCLUSION OptPRS predicted cognitive decline and AD phenotypes of cerebral organoids, supporting its use in risk assessments and drug-screening platform. 2025-08-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/59166 Title: Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4 Author(s): Lee, Se-In; Yu, Jichang; Lee, Hyein; Kim, Buyun; Jang, Min Jun; Jo, Hyeonbin; Kim, Na Yeon; Pak, Malk Eun; Kim, Jae Kwang; Cho, Sukhee; Won, Hong-Hee; Kim, Min Soo; Gao, Fan; Go, Younghoon; Seo, Jinsoo Abstract: The innate immune system can develop a form of memory called priming, where prior exposure to a stimulus enhances subsequent responses. While well-characterized in peripheral immunity, its function in brain-resident cells such as astrocytes under non-disease conditions remains unclear. Here we show that human astrocytes derived from the induced pluripotent stem cells of healthy female donors, but not microglia, acquire a primed state following transient immune stimulations. Upon subsequent exposure to amyloid-β (Aβ), these astrocytes secrete elevated levels of cytokines and promote microglial Aβ uptake. In contrast, astrocytes carrying the Alzheimer’s disease (AD) risk allele APOE4 exhibit reduced priming and fail to support microglial phagocytosis. These findings are validated in astrocyte-microglial co-cultures, cerebral organoids, and male mice, where astrocyte priming enhances Aβ clearance in an APOE4-sensitive manner. Our findings identify astrocytic immune memory as a modulator of microglial function and Aβ pathology, providing insights into how early protective responses in AD may be disrupted by genetic risk factors. 2025-07-31T15:00:00Z