Stem cell research & therapy · 2026
Dental pulp stem cells maintain epigenetic chromatin architecture remodeling primed by the etiological stimulus of biliary atresia.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sonoda Soichiro, Yu Liting, Dai Lisha, Kyumoto-Nakamura Yukari, Yoshimaru Koichiro, Yuniartha Ratih, Liu Ying, Sharifa M Majd, Murata Sara, Zakaria Mohammed Fouad, Kato Hiroki, Uehara Norihisa, Fukumoto Satoshi, Yamaza Haruyoshi, Matsuura Toshiharu, Taguchi Tomoaki, Tajiri Tatsuro, Yamaza Takayoshi
Аннотация
BACKGROUND: Biliary atresia (BA) is a nongenetic cholangiopathy characterized by biliary obliteration. However, the underlying pathological mechanism remains unclear. We aimed to explore the epigenetic BA pathology by using BA-specific deciduous dental pulp stem cells (BA-SHED), which develop in parallel with cholangiocyte progenitor cells in human embryos.
METHODS: BA-SHED were isolated from human exfoliated deciduous teeth of patients with BA using the colony-forming unit fibroblast method. After sequential stimulation with cytokines and chemicals in cultured BA-SHED, the in vitro bile duct-forming capacity was analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunofluorescence. Expression of hepatocyte nuclear factor 6 (HNF6) and transforming growth factor beta receptor 2 (TGFBR2) was analyzed using immunoblotting and RT-qPCR. The regulation of chromatin architecture at the HNF6 promoter was analyzed using nuclease-accessible chromatin-qPCR and chromatin immunoprecipitation-qPCR.
RESULTS: BA-SHED showed an inheritable increase in HNF6 levels, resulting in TGFBR2 suppression and deficiency in bile duct formation. BA-SHED also accumulated Brahma and P65 complexes around the HNF6 promoter with chromatin architecture remodeling. Tumor necrosis factor-alpha and interferon-gamma co-stimulation mimicked the epigenetic signatures of BA-SHED.
CONCLUSION: The present epigenetic memory in BA-SHED implies that BA-SHED imprint bile duct deficiency through TGFBR2 dysregulated by the HNF6 promoter activation epigenetically. Thus, BA-SHED are a potential model for expanding our knowledge in BA research.
METHODS: BA-SHED were isolated from human exfoliated deciduous teeth of patients with BA using the colony-forming unit fibroblast method. After sequential stimulation with cytokines and chemicals in cultured BA-SHED, the in vitro bile duct-forming capacity was analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunofluorescence. Expression of hepatocyte nuclear factor 6 (HNF6) and transforming growth factor beta receptor 2 (TGFBR2) was analyzed using immunoblotting and RT-qPCR. The regulation of chromatin architecture at the HNF6 promoter was analyzed using nuclease-accessible chromatin-qPCR and chromatin immunoprecipitation-qPCR.
RESULTS: BA-SHED showed an inheritable increase in HNF6 levels, resulting in TGFBR2 suppression and deficiency in bile duct formation. BA-SHED also accumulated Brahma and P65 complexes around the HNF6 promoter with chromatin architecture remodeling. Tumor necrosis factor-alpha and interferon-gamma co-stimulation mimicked the epigenetic signatures of BA-SHED.
CONCLUSION: The present epigenetic memory in BA-SHED implies that BA-SHED imprint bile duct deficiency through TGFBR2 dysregulated by the HNF6 promoter activation epigenetically. Thus, BA-SHED are a potential model for expanding our knowledge in BA research.