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| Status |
Public on Oct 13, 2023 |
| Title |
Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during fetal heart development [Multiome] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cardiomyocytes are highly metabolic cells responsible for generating the contractile force that drives heart function. During fetal development and regeneration, these cells undergo active division but lose their proliferation activity in the adult heart. The mechanisms that coordinate their metabolism and proliferation are not fully understood. Here, we study the developmental functions of the transcription factor NFYa, which we previously identified from regenerating cardiomyocytes. We show that loss of NFYa profoundly alters cardiomyocyte composition, with a decrease in immature regenerative cells and an increase in trabecular and mature cardiomyocytes, as revealed by spatial and single-cell transcriptome analyses. NFYa-deleted cardiomyocytes exhibited reduced proliferation and impaired mitochondrial metabolism, contributing to the cardiac growth defect. NFYa acts as a transcriptional activator of mitochondrial metabolic genes as well as cell-cycle genes in cardiomyocytes through its interaction with the cofactor SP2, providing a direct link between metabolism and proliferation at the gene transcriptional level. Our study reveals a key role of NFYa in regulating cardiac growth before birth and a previously unrecognized transcriptional control mechanism of metabolic genes in the heart, and highlights the importance of mitochondrial metabolism during fetal heart development and regeneration.
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| Overall design |
Examination of transcriptome and open chromatin changes in cardiomyocytes from WT and NFYa deleted E15.5 mouse hearts using multiome RNA and ATAC sequencing
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| |
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| Contributor(s) |
Cui M, Olson EN |
| Citation(s) |
37972593 |
| |
| Submission date |
May 19, 2023 |
| Last update date |
Apr 24, 2024 |
| Contact name |
Miao Cui |
| E-mail(s) |
miaocui713@gmail.com
|
| Phone |
6263768016
|
| Organization name |
UTSW
|
| Street address |
UT Southwestern Medical Center Department of Molecular Biology 6000 Harry Hines Blvd.
|
| City |
Dallas |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE232963 |
Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during fetal heart development |
|
| Relations |
| BioProject |
PRJNA974493 |
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