Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation
Institute of Aging · Chan Zuckerberg Biohub San Francisco
Abstract
Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq screening, we developed a systematic approach to identify single transcription factor (TF) perturbations that promote rejuvenation without dedifferentiation. Overexpressing E2F3 or EZH2, and repressing STAT3 or ZFX, reversed cellular hallmarks of aging-increasing proliferation, proteostasis, and mitochondrial activity, while decreasing senescence. EZH2 overexpression in vivo rejuvenated livers in aged mice, reversing aging-associated gene expression profiles, decreasing steatosis and fibrosis, and improving glucose tolerance. Mechanistically,…
Citation impact
- FWCI
- 107.10
- Percentile
- 100%
- References
- 46
Authors
9Topics & keywords
- Rejuvenation
- Transcription factor
- Reprogramming
- Transcription (linguistics)
- Cellular model
- Cell
- Gene expression
- Transcriptome