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| Status |
Public on Feb 14, 2019 |
| Title |
YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis in Vivo |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
Specialized adult somatic cells, such as cardiomyocytes (CMs), are highly differentiated with poor renewal capacity, an integral reason underlying organ failure in disease and aging. Among the least renewable cells in the human body, CMs renew approximately 1% annually. Consistent with poor CM turnover, heart failure is the leading cause of death. Here, we show that an active version of the Hippo pathway effector YAP, termed YAP5SA, partially reprograms adult mouse CMs to a more fetal and proliferative state. One week after induction, 19% of CMs that enter S-phase do so twice, CM number increases by 40%, and YAP5SA lineage CMs couple to pre-existing CMs. Genomic studies showed that YAP5SA increases chromatin accessibility and expression of fetal genes, partially reprogramming long-lived somatic cells in vivo to a primitive, fetal-like, and proliferative state.
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| Overall design |
We isolated cardiomyocyte nuclei from control and YAP5SA animals and performed nuclear RNA-seq (nucRNA-seq), ATAC-seq, and 4C-seq.
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| Contributor(s) |
Hill MC, Monroe TO, Martin JF |
| Citation(s) |
30773489 |
| Submission date |
Dec 06, 2018 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Matthew C Hill |
| E-mail(s) |
mhill@broadinstitute.org
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| Organization name |
Broad Institute of MIT and Harvard
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| Street address |
75 Aimes Street
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA508778 |
| SRA |
SRP172770 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123457_RAW.tar |
4.4 Gb |
(http)(custom) |
TAR (of BIGWIG, WIG) |
| GSE123457_TM_NucRNA_merged.txt.gz |
346.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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