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| Status |
Public on Jul 24, 2017 |
| Title |
Multi-cellular Transcriptional Profiling Reveals an Epigenetic Barrier to Adult Heart Regeneration [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background - The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. Methods - Cardiomyocytes, fibroblasts, leukocytes and endothelial cells from infarcted and non-infarcted neonatal (P1) and adult (P56) hearts were isolated by enzymatic dissociation and FACS. RNA sequencing (RNA-seq) was performed on these cell populations to generate a transcriptomic atlas of the major cardiac cell populations during cardiac development, repair and regeneration. In addition, we surveyed the epigenetic landscape of cardiomyocytes during post-natal maturation by performing deep sequencing of accessible chromatin regions using the Assay for Transposase-Accessible Chromatin (ATAC-seq) from purified cardiomyocyte nuclei (P1, P14 and P56). Results - Profiling of cardiomyocyte and non-myocyte transcriptional programs uncovered several injury responsive genes across regenerative and non-regenerative time points. However, the majority of transcriptional changes in all cardiac cell types resulted from developmental maturation from neonatal stages to adulthood rather than activation of a distinct regeneration-specific gene program. Furthermore, adult leukocytes and fibroblasts reverted to a neonatal state and re-activated a neonatal proliferative network following infarction. In contrast, cardiomyocytes failed to re-activate the neonatal proliferative network following infarction, which was associated with loss of chromatin accessibility around cell cycle genes during post-natal maturation. Conclusions – This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes.
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| Overall design |
Examination of RNA expression in developing cardiomyocytes isolated at P1 (day 1), P14 (day 14) and P56 (day 56 since birth) in biological triplicate
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| Contributor(s) |
Ziemann M, Sim CB, Quaife-Ryan GA, Kaspi A, Rafehi H, Ramialison M, El-Osta A, Hudson JE, Porrello ER |
| Citation(s) |
28733351 |
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| Submission date |
Mar 07, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Mark D Ziemann |
| E-mail(s) |
mark.ziemann@gmail.com
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| Organization name |
Deakin University
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| Department |
Life and Environmental Sciences
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| Street address |
75 Pigdons rd
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| City |
Waurn Ponds |
| State/province |
VIC |
| ZIP/Postal code |
3216 |
| Country |
Australia |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE95764 |
Multi-cellular Transcriptional Profiling Reveals an Epigenetic Barrier to Adult Heart Regeneration |
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| Relations |
| BioProject |
PRJNA378351 |
| SRA |
SRP101481 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE95762_cardiomycyte_rna.mx.txt.gz |
396.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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