May provide insight into birth defects, miscarriage and cancer – Zoo House News
- February 11, 2023
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Computer software developed at Washington University School of Medicine in St. Louis can predict what will happen to complex gene networks when individual genes are missing or selected more than usual. Such genetic networks play a key role in early embryonic development by directing stem cells to form specific cell types, which then form tissues and organs. Mapping the roles of individual genes in these networks is key to understanding healthy development and finding ways to regrow damaged cells and tissues. Likewise, understanding genetic errors could provide insights into birth defects, miscarriages, or even cancer.
Such genetic experiments – typically performed in the laboratory on animal models such as mice and zebrafish – have been a mainstay of developmental biology research for decades. Much can be learned about a gene’s function from experiments on animals in which a gene is missing or overexpressed, but these experiments are also expensive and time-consuming.
In contrast, newly developed software called CellOracle — detailed Feb. 8 in the journal Nature — can model hundreds of gene experiments in minutes, helping scientists identify key genes that play an important role in development, but potentially were overlooked by older, slower techniques. CellOracle is open source, with the code and information about the software available at this link.
“The scientific community has collected enough data from animal experiments that we can now do more than observe biological processes – we can create computer models of how genes interact with each other and predict what will happen if a gene is missing,” said the lead Author Samantha A. Morris, PhD, Associate Professor of Developmental Biology and Genetics. “And we can do this without experimental interference. Once we have identified an important gene, we still need to do the laboratory experiments to confirm the finding. But this computational method helps scientists narrow down the genes that matter most.”
CellOracle, featured in a recent technology feature in the journal Nature, is one of several relatively new software systems that have been developed to model insights into cellular gene regulation. Rather than simply identifying the networks, CellOracle is unique in its ability to let researchers test what happens when a network is disrupted in a specific way.
Morris and her team used the well-known developmental processes of blood cell formation in mice and humans and embryonic development in zebrafish to validate that CellOracle is working properly. Her studies, in collaboration with the lab of co-author and zebrafish developmental expert Lilianna Solnica-Krezel, PhD, the Alan A. and Edith L. Wolff Distinguished Professor and head of the Department of Developmental Biology, also uncovered new roles for certain genes in the Development of zebrafish that had not previously been identified.
And in a related article online in the journal Stem Cell Reports, Morris and her colleagues used CellOracle to predict what happens when specific genes are targeted beyond their usual expression levels.
“We found that if we target two specific genes, we can convert skin cells into a cell type that can repair damaged gut and liver,” Morris said. “In terms of regenerative medicine, these predictive tools are valuable for modeling how we can reprogram cells to become cell types that can promote healing after injury or disease.”
According to Morris, most laboratory methods for converting stem cells into other cell types, such as blood cells or liver cells, are inefficient. Maybe 2% of the cells arrive at the desired destination. Tools like CellOracle can help scientists identify which factors should be added to the cocktail to drive more cells into the desired cell type, e.g. B. those capable of repairing the intestines and liver.
Currently, CellOracle can model cell identity in more than 10 different species, including humans, mice, zebrafish, yeast, chicken, guinea pigs, rats, fruit flies, roundworms, the Arabidopsis plant, and two species of frogs.
“We get a lot of requests to add different species,” Morris said. “We’re working on adding axolotl, which is a type of salamander. They’re cool animals to study regeneration because they’re capable of regrowing entire limbs and other complex organs and tissues.”