Research Roundup: Fat Cell Hormone Slows Liver Tumor Growth and More Research News

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In this week’s research news, a fat hormone that slows liver tumor growth, a genetic map to track tumorigenesis, study that shows we inherit more than expected epigenetic information from our mothers, Alzheimer linked APOE gene protects against glaucoma.

Fat Hormone Slows Liver Tumor Growth

Scientists at the University of Michigan Life Sciences Institute found that a hormone secreted by fat cells could slow the growth of liver tumors in mice. The research team previously used single-cell RNA sequencing to construct a liver cell atlas and map intercellular signaling in healthy and NASH mouse livers. NASH stands for nonalcoholic steatohepatitis, a type of fatty liver disease. Working to identify specific molecular changes in the NASH state of the liver cell types, they found changes in two types of immune cells that seemed to lead to the development of hepatocellular carcinoma (HCC), the most common type of liver cancer. This seemed to occur in T cells and macrophages, showing signs of acquired molecular features associated with cancer. They also identified a hormone, NRG4, secreted by fat cells that appears to protect mouse livers against NASH and HCC. By boosting NRG4 levels in the mice, they suppressed NASH liver cancer progression.

Do We Inherit More Epigenetic Information than We Think?

Researchers from the Walter and Eliza Hall Institute in Melbourne, Australia, found that more epigenetic information is carried from mother to offspring than was previously understood. They published their research in Nature Communications.

Epigenetics is how expression of genes are switched on and off. One way this occurs, is through addition of methyl groups (a carbon atom with three hydrogen atoms attached) to the  genes. Under certain situations and environments, these genes are switched on or off. These changes could be diet, trauma, whether the genes or gene alterations are inherited from the mother or the father, or other factors. But the genes were generally believed to be reset when they are passed on to offspring. 

Part of the team's research found that a specific protein in the mother's egg can affect the genes behind the skeletal patterning of offspring. SMCHD1 is an epigenetic regulator discovered in 2008. Hox genes, which are essential for normal skeletal development control the identity of each vertebra during embryonic development. SMCHD1 prevents the Hox genes from activating too soon. They found that the amount of SMCHD1 in the mother's egg affects Hox gene activity and influences the patterning of the embryos. Without maternal SMCHD1 in the egg, offspring were born with altered skeletons.

"It took us a while to process because our discovery was unexpected," Marnie Blewitt, Ph.D., chief investigator and Joint Head of the Epigenetics and Development Division at WEHI, said. "Knowing that epigenetic information from the mother can have effects with life-long consequences for body patterning is exciting, as it suggests this is happening far more than we ever thought. It could open a Pandora's box as to what other epigenetic information is being inherited."

A Genetic Map of Tumors Show How They Grow

Researchers at the University of Oxford used a new technique called spatial transcriptomics to map out the genetic changes of a whole prostate, including both healthy and cancerous cells. The technique grouped cells according to similar genetic identities. Surprisingly, they found that areas of what were thought to be healthy tissue already had genetic characteristics of cancer. What was originally thought to be healthy tissue showed mutations specifically linked to cancer. Researchers also analyzed more than 150,000 regions including prostate, breast cancer, skin, lymph node and brain tissue. They then developed an algorithm to track groups of cells with similar genetic changes in their specific location.

Alzheimer's Linked APOE Gene and Glaucoma Protection

The most prominent gene associated with the risk of Alzheimer's disease is the APOE4 gene variant. However, this same gene variant decreases the risk of glaucoma, an eye disease. Researchers at Mass Eye and Ear and Brigham and Women's Hospital and Mass General Brigham also prevented the destruction of neurons in the eyes of mice with glaucoma by using a drug that targeted the APOE signaling pathway. Specifically, APOE4 blocks a disease cascade that causes the destruction of retinal ganglion cells in glaucoma. Separately, in a mouse model, they used a drug called Galectin-3, which is regulated by the APOE gene, to prevent the death of retinal ganglion cells, which cause loss of vision in glaucoma.

"Our research provides greater understanding of the genetic pathway that leads to irreversible blindness in glaucoma, and importantly, points to a possible treatment to address the root cause of the vision loss," Milica Margeta, M.D., Ph.D., lead author and a glaucoma specialist and scientist at Mass Eye and Ear, and assistant professor of ophthalmology at Harvard Medical School, said. "This study shows that the APOE-mediated disease cascade is clearly harmful in glaucoma, and that when you interfere with it genetically or pharmacologically, you can actually stop the disease

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