Адгезионная и транскрипционная функции ?-катенина в самообновлении эмбриональных стволовых клеток мыши
Диссертация
Ингибиторы GSK3 способствуют становлению и поддержанию плюрипотентности, и их положительное влияние на самообновление в значительной степени опосредованы ß—катенином (Wray et al., 2011). Известно также, что инактивация GSK3 наиболее эффективно способствует поддержанию плюрипотентности в сочетании с применением ингибиторов MEK/ERK каскада, в то время, как само по себе ингибирование GSK3… Читать ещё >
Содержание
- Список используемых сокращений
- Актуальность проблемы
- Цели и задачи исследования
- ОБЗОР ЛИТЕРАТУРЫ
- 1. Эмбриональные стволовые клетки: регуляция самообновления и плюрипотентности
- 1. 1. Происхождение и свойства ЭСК
- 1. 2. Транскрипционные факторы, регулирующие плюрипотентность и самообновление ЭСК
- 1. 3. Сигнальные пути, регулирующие самообновление и плюрипотентность ЭСК
- 1. 4. Особенности регуляции клеточного цикла ЭСК мыши
- 1. 5. Индукция дифференцировки ЭСК
- 2. Адгезионная и транскрипционная функции р-катенина
- 2. 1. Р-катенин и его роль в каноническом Wnt-сигнальном каскаде и межклеточной адгезии
- 2. 2. Функции р-катенина в эмбриогенезе, клеточной пролиферации и дифференцировке
- 2. 3. Роль Р-катенина и его партнеров в регуляции плюрипотентности, самообновления и дифференцировки
- МАТЕРИАЛЫ И МЕТОДЫ
- Культивирование клеток
- МТТ-тест и кривые роста
- Временная трансфекция и анализ люциферазной активности
- Проточная цитофлуориметрия на содержание ДНК
- Анализ активности каспаз in vitro
- Иммунофлуоресценция
- Экстракция тотального белка в денатурирующих условиях и Вестерн блоттинг 46 Экстракция белка для иммунопреципитации и осаждения GST-E-кадгерином
- Экстракция РНК и ОТ-ПЦР
- РЕЗУЛЬТАТЫ
- Общая характеристика активности Р-катенина и экспрессия его коактиваторов в недифференцированных мЭСК и при дифференцировке
- Уровень экспрессии, локализация и транскрипционная активность р-катенина при инактивации GSK3 в недифференцированных мЭСК
- Влияние инактивации GSK3 на Р-катенин-зависимую адгезию в недифференцированных мЭСК
- Регуляция маркеров ЭМП при инактивации GSK3 в недифференцированных мЭСК и при дифференцировке
- Влияние ингибиторов GSK3 на выживаемость, пролиферацию и экспрессию регуляторов клеточного цикла в мЭСК
- Влияние инактивации GSK3 на экспрессию фактора REST в мЭСК
- Модуляция экспрессии и активности Р-катенина ингибитором MEK/ERK каскада
- ОБСУЖДЕНИЕ
- Активность Р-катенина в недифференцированных мЭСК и при дифференцировке
- Адгезионный пул Р-катенина и межклеточная адгезия
- Сигнальный пул р-катенина и избирательная активация транскрипции
- Модуляция экспрессии и активности Р-катенина ингибитором МЕК/ЕЮС каскада
- Влияние ингибиторов вЭКЗ на выживание и пролиферацию мЭСК
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- Сердечно благодарю мою семью и друзей, поддержка которых очень много для меня значит.