Journal article
Intestinal stem cell aging signature reveals a reprogramming strategy to enhance regenerative potential
CM Nefzger, T Jardé, A Srivastava, J Schroeder, FJ Rossello, K Horvay, M Prasko, JM Paynter, J Chen, CF Weng, YBY Sun, X Liu, E Chan, N Deshpande, X Chen, YJ Li, J Pflueger, RM Engel, AS Knaupp, K Tsyganov Show all
Npj Regenerative Medicine | Published : 2022
Open access
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.
Grants
Awarded by State Government of Victoria
Funding Acknowledgements
We acknowledge the high quality scientific and technical assistance of the Flowcore Facility, Histology Platform and BDI Organoid Program at Monash University. The authors thank the ACRF Center for Cancer Genomic Medicine at the MHTP Medical Genomics Facility and the Monash Micromon Genomics Facility for assistance with next generation library preparation and Illumina sequencing. We also thank Monash Animal Services, in particular Jennifer Flores, Monique Centrone and Jessica Hatwell-Humble for help with animal husbandry. This work was supported by NHMRC project grants to J.M. Polo and H.E.A. (APP1061883), HEA (APP1188689), C.M.N. (APP1146623) and T.J. (APP1129600) and seed funding from the Monash University Strategic Grant scheme to C.M.N. and K.H.; J.M. Polo was supported by a Sylvia and Charles Senior Medical Viertel Fellowship and A.S.K. by an NHMRC Early Career Fellowship (APP1092280). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.