Related Experiment Video
Updated: Oct 28, 2025
09:16
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
7.4K
Mitogen-induced transcriptional programming in human fibroblasts
Kiran L Sharma1, Shuo Jia1, Tasnim H Beacon2
1Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
Gene
|July 18, 2021
Summary
Mitogen- and stress-activated kinases (MSK) regulate gene expression during cell proliferation. This study used RNA sequencing to identify immediate-early genes controlled by MSK, revealing MSK
Area of Science:
- Cell Biology
- Molecular Biology
- Gene Regulation
Background:
- The RAS-MAPK pathway controls cell proliferation by initiating gene transcription.
- Mitogen- and stress-activated kinases (MSK) 1 and 2 phosphorylate histone H3, facilitating transcription of immediate-early genes.
- Understanding MSK's role in gene regulation is crucial for deciphering proliferation control.
Purpose of the Study:
- To investigate the role of MSK in regulating immediate-early gene expression.
- To identify specific genes whose induction is dependent on MSK activity.
- To differentiate MSK-dependent from MSK-independent transcriptional responses.
Main Methods:
- Transcriptome analysis using RNA sequencing on human fibroblast cells (CCD-1070Sk).
- Stimulation of cells with epidermal growth factor (EGF) or phorbol ester (TPA).
- Inhibition of MSK/PKA activity using H89 and Rp-cAMPS.
Main Results:
- Many immediate-early genes were induced independently of MSK activity.
- MSK inhibition with H89 attenuated the induction of several immediate-early genes, a finding corroborated by PKA inhibition.
- H89, but not Rp-cAMPS, further upregulated EGF-induced transcriptional repressor genes, suggesting MSK modulates their induction levels.
Conclusions:
- MSK plays a role in modulating the induction of specific immediate-early genes, including transcriptional repressors.
- The study distinguishes MSK-dependent and independent pathways in immediate-early gene regulation.
- Findings contribute to understanding the intricate mechanisms of cell proliferation control.
Related Concept Videos
01:24Methods of Nuclear Reprogramming
1.9K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.9K
01:29Somatic to iPS Cell Reprogramming
2.4K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.4K
01:09Introduction to Fibroblasts
3.3K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.3K
02:38Mitogens and the Cell Cycle
7.2K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.2K
01:06Induced Pluripotent Stem Cells
4.7K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.7K
01:16TGF - β Signaling Pathway
8.1K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.1K