Multi-omic rejuvenation of human cells by maturation phase transient reprogramming
- Epigenetics Programme, Babraham Institute, United Kingdom
- Imaging Facility, Babraham Institute, United Kingdom
- Chronomics Limited, United Kingdom
- Laboratory for Epigenetic Mechanisms/Chromosome Dynamics Lab, Instituto Gulbenkian de Ciência, Portugal
- Wellcome Trust Sanger Institute, Hinxton, United Kingdom
- Centre for Trophoblast Research, University of Cambridge, United Kingdom
Figures
Figure 1 with 1 supplement
Transiently reprogrammed cells reacquire their initial cellular identity.
(A) Mean DNA methylation age (calculated using the multi-tissue clock; Horvath, 2013) throughout the reprogramming process where cells were transduced with our tetO-GFP-hOKMS vector and treated …
Figure 1—figure supplement 1
Transiently reprogrammed cells reacquire their initial cellular identity.
(A) Mean DNA methylation age (calculated using multiple epigenetic clocks; Hannum et al., 2013; Horvath et al., 2018; Weidner et al., 2014; Yang et al., 2016; Lu et al., 2019a; Levine et al., 2018) …
Figure 2 with 1 supplement
Epigenetic memory at enhancers and persistent fibroblast gene expression may allow cells to return to their initial identity.
(A) The mean expression levels of fibroblast-specific and iPSC-specific gene sets during transient reprogramming and complete reprogramming. Error bars represent the standard deviation. (B) Heatmap …
Figure 2—figure supplement 1
Epigenetic memory at enhancers and persistent fibroblast gene expression may allow cells to return to their initial identity.
(A) Volcano plot showing the differentially expressed genes between iPSCs and fibroblasts. Differentially expressed genes were determined with DESeq2 (p≤0.05 and log2 fold change≤1). In this …
Figure 3 with 1 supplement
Transient reprogramming reverses age-associated changes in the transcriptome and partially restores fibroblast migration speed.
(A) Principal component analysis (PCA) of fibroblast aging-associated gene expression levels in transient reprogramming (magenta) and reference aging fibroblast samples (light blue-dark blue). …
Figure 3—figure supplement 1
Transient reprogramming reverses age-associated changes in the transcriptome and partially restores fibroblast migration speed.
(A) Results of the tenfold cross validation comparing predicted age to actual age for a custom transcriptome clock. (B) Mean transcription age calculated using a custom transcriptome clock (median …
Figure 4 with 1 supplement
Optimal transient reprogramming can reverse age-associated changes in the epigenome.
(A) Boxplots of the levels of H3K9me3 in individual cells calculated based on fluorescence intensity within nuclei (segmented using DAPI). The levels of H3K9me3 were found to decrease with age and …
Figure 4—figure supplement 1
Optimal transient reprogramming can reverse age-associated changes in the epigenome.
(A) The expression levels of DNA methyltransferases and TET enzymes throughout the reprogramming process where cells were transduced with our tetO-GFP-hOKMS vector and treated continuously with …
Author response image 1
Additional files
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Supplementary file 1
A comparison of previous transient reprogramming methods.
- https://cdn.elifesciences.org/articles/71624/elife-71624-supp1-v2.xlsx
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Supplementary file 2
The complete results of the Tukey’s range test that was used to compare the morphology ratio between the different stages and groups of MPTR.
- https://cdn.elifesciences.org/articles/71624/elife-71624-supp2-v2.xlsx
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Supplementary file 3
The lists of fibroblast genes that were identified to either temporarily downregulate, temporarily upregulate or persist in their expression during MPTR.
- https://cdn.elifesciences.org/articles/71624/elife-71624-supp3-v2.xlsx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/71624/elife-71624-transrepform1-v2.docx
