Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01921-6
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Funding
- AXA research fund
- Fundacao para a Ciencia e Tecnologia (FCT)
- FEDER [PTDC/BIM-MED/0032/2014, PTDC/BEX-BCM/5899/2014, LISBOA-01-0145-FEDER-007391]
- FEDER, through POR Lisboa-Programa Operacional Regional de Lisboa
- Fundacao para a Ciencia e a Tecnologia
- Fundação para a Ciência e a Tecnologia [PTDC/BIM-MED/0032/2014, PTDC/BEX-BCM/5899/2014] Funding Source: FCT
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Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here, we report that fibroblasts from old mice express higher levels of Zeb2, a transcription factor that activates epithelial-to-mesenchymal transition. Synthesis of Zeb2 protein is controlled by a natural antisense transcript named Zeb2-NAT. We show that transfection of adult fibroblasts with specific LNA Gapmers induces a robust downregulation of Zeb2-NAT transcripts and Zeb2 protein and enhances the reprogramming of old fibroblasts into pluripotent cells. We further demonstrate that Zeb2-NAT expression is precociously activated by differentiation stimuli in embryonic stem (ES) cells. By knocking down Zeb2-NAT, we were able to maintain ES cells challenged with commitment signals in the ground state of pluripotency. In conclusion, our study identifies a long noncoding RNA that is overlapping and antisense to the Zeb2 locus as a target for rejuvenation strategies.
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