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.

Details

Title
Intestinal stem cell aging signature reveals a reprogramming strategy to enhance regenerative potential
Author
Nefzger, Christian M. 1   VIAFID ORCID Logo  ; Jardé, Thierry 2 ; Srivastava, Akanksha 3 ; Schroeder, Jan 4   VIAFID ORCID Logo  ; Rossello, Fernando J. 4 ; Horvay, Katja 2 ; Prasko, Mirsada 2 ; Paynter, Jacob M. 4 ; Chen, Joseph 4 ; Weng, Chen-Fang 2 ; Sun, Yu B. Y. 5 ; Liu, Xiaodong 4 ; Chan, Eva 2   VIAFID ORCID Logo  ; Deshpande, Nikita 6 ; Chen, Xiaoli 6 ; Li, Y. Jinhua 5 ; Pflueger, Jahnvi 7 ; Engel, Rebekah M. 8 ; Knaupp, Anja S. 4 ; Tsyganov, Kirill 9 ; Nilsson, Susan K. 10   VIAFID ORCID Logo  ; Lister, Ryan 7 ; Rackham, Owen J. L. 11 ; Abud, Helen E. 2   VIAFID ORCID Logo  ; Polo, Jose M. 12   VIAFID ORCID Logo 

1  Monash University, Department of Anatomy and Developmental Biology, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Australian Regenerative Medicine Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
2  Monash University, Department of Anatomy and Developmental Biology, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Cancer Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
3  The University of Western Australia, Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
4  Monash University, Department of Anatomy and Developmental Biology, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Australian Regenerative Medicine Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
5  Monash University, Department of Anatomy and Developmental Biology, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
6  University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
7  The University of Western Australia, Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Harry Perkins Institute of Medical Research, Nedlands, Australia (GRID:grid.431595.f) (ISNI:0000 0004 0469 0045) 
8  Monash University, Department of Anatomy and Developmental Biology, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Cabrini Hospital, Cabrini Monash University Department of Surgery, Malvern, Australia (GRID:grid.440111.1) (ISNI:0000 0004 0430 5514) 
9  Monash University, Monash Bioinformatics Platform, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
10  Monash University, Australian Regenerative Medicine Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Biomedical Manufacturing CSIRO, Clayton, Australia (GRID:grid.1002.3) 
11  Duke-National University of Singapore Medical School, Program in Cardiovascular and Metabolic Disorders, Singapore, Singapore (GRID:grid.428397.3) (ISNI:0000 0004 0385 0924) 
12  Monash University, Department of Anatomy and Developmental Biology, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Australian Regenerative Medicine Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); Monash University, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); The University of Adelaide, Adelaide Centre for Epigenetics, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304); The University of Adelaide, The South Australian Immunogenomics Cancer Institute, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20573995
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41536-022-00226-7
ProQuest document ID
2677214061
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.