A gene that scientific dogma insists is inactive in adults actually plays a vital role in preventing the underlying cause of most heart attacks and strokes, researchers at the University of Virginia School of Medicine have determined. The discovery opens a new avenue for battling those deadly conditions, and it raises the tantalizing prospect that doctors could use the gene to prevent or delay at least some of the effects of aging.
“Finding a way to augment the expression of this gene in adult cells may have profound implications for promoting health and possibly reversing some of the detrimental effects with aging,” said researcher Gary K. Owens, PhD, director of UVA’s Robert M. Berne Cardiovascular Research Center.
Unexpected Protective Effect
The gene, Oct4, plays a key role in the development of all living organisms, but scientists have, until now, thought it was permanently inactivated after embryonic development. Some controversial studies have suggested it might have another function later in life, but the UVA researchers are the first to provide conclusive evidence of that: Owens and his colleagues have determined the gene plays a critical protective role during the formation of atherosclerotic plaques inside blood vessels. The rupturing of these plaques is the underlying cause of many heart attacks and strokes.
The researchers found that Oct4 controls the movement of smooth muscle cells into protective fibrous “caps” inside the plaques – caps that make the plaques less likely to rupture. The researchers also have provided evidence that the gene promotes many changes in gene expression that are beneficial in stabilizing the plaques.
This is exciting, because studies suggest that it may be possible to develop drugs or other therapeutic agents that target the Oct4 pathway as a means to reduce the incidence of heart attacks or stroke. “Our findings have major implications regarding possible novel therapeutic approaches for promoting stabilization of atherosclerotic plaques,” said Olga A. Cherepanova, PhD, a senior research scientist in Owens’ lab.
One surprising finding from UVA’s research: When the researchers blocked the effect of Oct4 in mice, they thought the atherosclerotic plaques might become smaller, because of the reduced number of smooth muscle cells inside. Instead, the plaques grew larger, less stable and more dangerous, stuffed with lipids, dead cells and other damaging components.
Advancing Regenerative Medicine
While UVA’s research has focused on how Oct4 offers cardiovascular protection, Owens and his colleagues believe the gene could also prove critical to the field of regenerative medicine, which investigates the growth and replacement of tissues and organs. The researchers believe that Oct4 and its family of target genes are activated in other somatic cells – the non-reproductive cells in the body – and play a key role in the cells’ ability to repair damage and heal wounds. Studies to test this are under way in Owens’ lab.
Oct4 is one of the “stem cell pluripotency factors” described by Shinya Yamanaka, MD, PhD, for which he received the 2012 Nobel Prize. His lab and many others have shown that artificial over-expression of Oct4 within somatic cells grown in a lab dish is essential for reprogramming these cells into induced pluripotential stem cells, which can then develop into any cell type in the body or even an entire organism.
The UVA researchers suspect that at least some of the detrimental effects of aging, including the increased possibility of a plaque rupture, stem from a decrease in the body’s ability to reactivate Oct4. “Finding a way to reactivate this pathway may have profound implications for health and aging,” Owens said. “We think this is just the tip of the iceberg for controlling plasticity of somatic cells, and this could impact many human diseases and the field of regenerative medicine. Who knows, this may end up being the ‘fountain-of-youth gene,’ a way to revitalize old and worn-out cells. Only time will tell.”
The Latest on: Oct4 gene
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The Latest on: Oct4 gene
- Ectopic activation of WNT signaling in human embryonal carcinoma cells and its effects in short- and long-term in vitro cultureon August 15, 2019 at 2:44 am
In TGCCs, global gene expression profiling together with β-catenin immunohistochemical ... We collected cell-samples every 5 passages and analyzed the dynamics of OCT4/SSEA4 and in response to ...
- Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung canceron August 9, 2019 at 2:39 am
The contribution of Oct4 in the upregulation of Egr1 and its downstream gene OPN was further verified in H1299 cells transduced with LV.shOct4 or LV.shLuc. Although the efficiency of Oct4 knockdown ...
- Genes that Control Pluripotencyon May 20, 2019 at 5:56 pm
OCT4 can also affect gene expression by forming a complex with SOX2 in the cell nucleus. This is important both in maintaining pluripotency and determining lineage specialization. This function can be ...
- Effect of overexpression of Oct4 and Sox2 genes on the biological and oncological characteristics of gastric cancer cellson March 22, 2019 at 5:00 pm
1 Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, People’s Republic of China; 2 Department of Clinical ...
- Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesison February 27, 2019 at 2:35 am
Octamer-binding transcription factor 4 (Oct4) is a stem cell pluripotency gene critical for maintenance of pluripotency in the inner cell mass of the blastocyst 1. Oct4 expression is tightly regulated ...
- Eugene 'Gene' L. Simmonson October 5, 2018 at 5:00 pm
MARION — Eugene “Gene” L. Simmons, 85, of Roebuck, South Carolina, husband of Lyda Pickett Simmons, died Thursday, Oct. 4, 2018. Gene was born May 6, 1933, to the late Theron and Lela Goley Simmons.
- Viruses affected gene flow between humans, Neanderthalson October 4, 2018 at 12:48 pm
Oct. 4 (UPI) --Previous studies have confirmed interbreeding among humans and Neanderthals. Now, a new genetic survey has revealed gene flow between humans and Neanderthals was mediated by viral ...
- CRISPR Activation of Single Genes Turns Skin Cells to Stem Cellson January 19, 2018 at 2:25 am
This technique, which incorporates a modified form of CRISPR gene-editing systems Cas9 enzyme, allowed Dr. Ding and colleagues to target and epigenetically remodel specific genomic locations: the Oct4 ...
- 'Knockout' Studies Now Disabling Genes in Human Embryoson October 10, 2017 at 9:12 am
But of course, people aren’t mice. Numerous examples exist of the eradication of equivalent genes in both species that result in different effects for each. As expected, losing Oct4 was catastrophic ...
- UK gene editing breakthrough could land an Aussie in jail for 15 years: here’s why our laws need to catch upon September 25, 2017 at 8:37 pm
Niakan’s team showed that one particular gene, “OCT4”, plays a key role. They used the CRISPR-CAS9 system – which allows researchers to make precise changes to DNA sequences - to turn off the OCT4 ...
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