Taipei Veterans General Hospital

Yueh Chien

Shih-Hwa Chiou

Yi-Ping Yang

Guang-Yuh Chiou

Ping-Hsing Tsai

Shih-Jie Chou

The present invention provides a method for rescuing retinal degeneration comprising administering a subject in need thereof a pharmaceutical composition comprising an inhibitor of DUSP6 via ERK 1/2 autophagy pathway.

Method and pharmaceutical composition for rescuing retinal degeneration

The preset invention relates to a novel super-enhancer-bound Ash2l/OSN complex that can drive enhance activation, govern pluripotency network and sternness circuitry, and a reprogramming system or method through the regulation of this super-enhancer, Ash2l, to modulate pluripotency and cell fates. Ash2l directly binds to super-enhancers of several stemness genes to regulate pluripotency and self-renewal in pluripotent stem cells. Ash2l recruits Oct4/Sox2/Nanog (OSN) to form Ash2l/OSN complex at the super-enhancers of Jarid2, Nanog, Sox2, and Oct4, and further drives enhancer activation, upregulation of stemness genes, and maintains the pluripotent circuitry. Ash2l knockdown abrogates the OSN recruitment to all super-enhancers and further hinders the enhancer activation. In addition, CRISPRi/dCas9-mediated blocking of Ash2l-binding motifs at these super-enhancers also prevents OSN recruitment and enhancer activation, validating that Ash2l directly binds to super-enhancers and initiates the pluripotency network. Transfection of Ash2l with W118A mutation to disrupt Ash2l-Oct4 interaction fails to rescue Ash2l-driven enhancer activation and pluripotent gene upregulation in Ash2l-depleted pluripotent stem cells.

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Taipei, Taiwan

Yueh Chien