簡介:
- 作者: Yinghua Huang, Hui Zhang, Lulu Wang, Chuanqing Tang, Xiaogan Qin, Xinyu Wu, Meifang Pan,Yujia Tang, Zhongzhou Yang, Isaac A. Babarinde, Runxia Lin, Guanyu Ji, Yiwei Lai, Xueting Xu, Jianbin Su, Xue Wen, Takashi Satoh, Tanveer Ahmed, Vikas Malik, Carl Ward, Giacomo Volpe, Lin Guo, Jinlong Chen, Li Sun, Yingying Li, Xiaofen Huang, Xichen Bao, Fei Gao, Baohua Liu, Hui Zheng, Ralf Jauch, Liangxue Lai, Guangjin Pan, Jiekai Chen, Giuseppe Testa, Shizuo Akira, Jifan Hu, Duanqing Pei, Andrew P. Hutchins, Miguel A. Esteban, and Baoming Qin
- 雜志: Nat Commun
- Doi: https://www.doi.org/10.1038/s41467-020-18900-z
- 出版日期: 2020 Oct 8
論文中使用的產品/服務
Quotation shows PackGene:For the reprogramming of Jmjd3 cKO MEFs, Jmjd3fl/fl MEFs at P1 were infected with Cre or control RFP adeno-associated viruses (PackGene) for 24 h to complete JMJD3 JmjC domain deletion and then these cells were reprogrammed to pluripotency colonies in standard way.
Research Field:reprogramming
摘要
The interplay between the Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and transcriptional/epigenetic co-regulators in somatic cell reprogramming is incompletely understood. Here, we demonstrate that the histone H3 lysine 27 trimethylation (H3K27me3) demethylase JMJD3 plays conflicting roles in mouse reprogramming. On one side, JMJD3 induces the pro-senescence factor Ink4a and degrades the pluripotency regulator PHF20 in a reprogramming factor-independent manner. On the other side, JMJD3 is specifically recruited by KLF4 to reduce H3K27me3 at both enhancers and promoters of epithelial and pluripotency genes. JMJD3 also promotes enhancer-promoter looping through the cohesin loading factor NIPBL and ultimately transcriptional elongation. This competition of forces can be shifted towards improved reprogramming by using early passage fibroblasts or boosting JMJD3's catalytic activity with vitamin C. Our work, thus, establishes a multifaceted role for JMJD3, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription.
關于派真
作為一家專注于AAV 技術十余年，深耕基因治療領域的CRO&CDMO，派真生物可提供從載體設計、構建到 AAV、慢病毒和 mRNA 服務的一站式解決方案。憑借深厚的技術實力、卓越的運營管理和高標準的服務交付，我們為全球客戶提供一站式CMC解決方案，包括從早期概念驗證、成藥性評估到IIT、IND及BLA的各個階段。
?
憑借我們獨立知識產權的π-alphaTM 293 細胞AAV高產技術平臺，我們能將AAV產量提高多至10倍，每批次產量可達1×101?vg，以滿足多樣化的商業化和臨床項目需求。此外，我們定制化的mRNA和脂質納米顆粒（LNP）產品及服務覆蓋藥物和疫苗開發的各個階段，從研發到符合GMP的生產，提供端到端的一站式解決方案。
