Related Experiment Video
Updated: Jul 21, 2026
08:42
Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
Published on: August 28, 2016
27.2K
AP-1 activation mediates post-natal cardiomyocyte maturation.
Hongjie Zhang1, Lijuan Pei1, Zhaohui Ouyang1
1Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Department of Molecular and Cellular Biology, Tongji University, Shanghai 200092, China.
Cardiovascular Research
|May 31, 2022
Summary
Activating protein 1 (AP-1) transcription factors promote cardiomyocyte maturation by regulating fatty acid metabolism. Inhibiting AP-1 in neonatal mice hinders this crucial developmental process.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Developmental Biology
Background:
- Post-natal cardiomyocyte maturation involves cell cycle exit, binucleation, and metabolic shifts.
- The molecular triggers and transcriptional programs governing this maturation are not fully elucidated.
Purpose of the Study:
- To identify key factors regulating post-natal cardiomyocyte maturation using single-cell RNA sequencing.
- To investigate the role of Activating Protein 1 (AP-1) transcription factors in this process.
Main Methods:
- Single-cell RNA sequencing of post-natal rat hearts at Day 1 and Day 7.
- In vitro manipulation of AP-1 activity using chemical activators (palmitate, adrenergic stimulation) and knockdown of specific AP-1 members (Atf3, Jun).
- In vivo assessment of AP-1 inhibition using T-5224 in neonatal mice.
Main Results:
- Transient upregulation of AP-1 transcription factors observed in maturing cardiomyocytes.
- AP-1 activation inhibited cardiomyocyte cytokinesis and promoted maturation.
- Knockdown of AP-1 members (Atf3, Jun) promoted cytokinesis and inhibited maturation.
- AP-1 activation of fatty acid metabolic genes was identified as a key mechanism.
- AP-1 inhibition in vivo impaired cardiomyocyte maturation.
Conclusions:
- AP-1 transcription factors are critical regulators of post-natal cardiomyocyte maturation.
- This study provides novel insights into the molecular mechanisms of heart development.
- Findings suggest potential therapeutic targets for congenital heart diseases.
Related Concept Videos
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:18Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...