Artificial Genes Help Understand How Cells Learn Their Location in the Body – Technology Networks

stemadminJuly 7, 2022Stem Cell ResearchNo comments

Researchers at New York University have created artificialHoxgeneswhich plan and direct where cells go to develop tissues or organsusing new synthetic DNA technology and genomic engineering in stem cells.

Their findings,published inScience, confirm how clusters ofHoxgenes help cells to learn and remember where they are in the body.

IfHoxgenes fail through misregulation or mutation, cells can get lost, playing a role in some cancers, birth defects, and miscarriages.

I dont think we can understand development or disease without understandingHoxgenes, saidEsteban Mazzoni, associate professor of biology at NYU and the studys co-senior author.

Despite their importance in development,Hoxgenes are challenging to study. They are tightly organized in clusters, with onlyHoxgenes in the piece of DNA where they are found and no other genes surrounding them (what scientists call a gene desert). And while many parts of the genome have repetitive elements,Hoxclusters have no such repeats. These factors make them unique but difficult to study with conventional gene editing without affecting neighboringHoxgenes.

We are very good at reading the genome, or sequencing DNA. And thanks to CRISPR, we can make small edits in the genome. But were still not good at writing from scratch, explained Mazzoni. Writing or building new pieces of the genome could help us to test for sufficiencyin this case, find out what the smallest unit of the genome is necessary for a cell to know where it is in the body.

Mazzoni teamed upJef Boeke, director of the Institute of System Genetics at NYU Grossman School of Medicine, who is known for his work synthesizing a synthetic yeast genome. Boekes lab was looking to translate this technology to mammalian cells.

Graduate student Sudarshan Pinglay in Boekes lab fabricated long strands of synthetic DNA by copying DNA from theHoxgenes of rats. The researchers then delivered the DNA into a precise location within pluripotent stem cells from mice. Using the different species enabled the researchers to distinguish between the synthetic rat DNA and the natural cells of mice.

Dr. Richard Feynman famously opined, What I cannot create, I do not understand. We are now a giant step closer to understandingHox, said Boeke, who is also a professor of biochemistry and molecular pharmacology at NYU Grossman and is the studys co-senior author.

The researchers discovered that these gene-dense clusters alone contain all of the information needed for cells to decode a positional signal and remember it. This suggests that the compact nature ofHoxclusters is what helps cells learn their location, confirming a long-standing hypothesis onHoxgenes that was previously difficult to test.

The creation of synthetic DNA and artificialHoxgenes paves the way for future research on animal development and human diseases.

Different species have different structures and shapes, a lot of which depends on howHoxclusters get expressed. For instance, a snake is a long thorax with no limbs, while a skate has no thorax and is just limbs. A better understanding ofHoxclusters may help us to understand how these systems get adapted and modified to make different animals, said Mazzoni.

More broadly, this synthetic DNA technology, for which we have built a kind of factory, will be useful for studying diseases that are genomically complicated and now we have a method for producing much more accurate models for them, said Boeke.

Reference:Pinglay S, Bulaji M, Rahe DP, et al. Synthetic regulatory reconstitution reveals principles of mammalian Hox cluster regulation. Science. 2022;377(6601):eabk2820. doi: 10.1126/science.abk2820

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