Intestinal stem cell aging signature reveals a reprogramming strategy to enhance regenerative potential
Christian M. Nefzger, Thierry Jardé, Akanksha Srivastava, Jan Schröder, Fernando J. Rossello, Katja Horvay, Mirsada Prasko, Jacob M. Paynter, Joseph Chen, Chen-Fang Weng, Yu Sun, Xiaodong Liu, Eva L. Chan, Nikita Deshpande, Xiaoli Chen, Y. Jinhua Li, Jahnvi Pflueger, Rebekah Engel, Anja S. Knaupp, Kirill Tsyganov, Susan K. Nilsson, Ryan Lister, Owen J. L. Rackham, Helen E. Abud, José M. Polo
Abstract
The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorithm, we identified a set of key transcription factors (Egr1, Irf1, FosB) that drives molecular and functional differences between old and young states. Overall, by dissecting the molecular signature of aged ISCs, our study identified transcription factors that enhance the regenerative capacity of ISCs.