Animals are expected to contain the secret of human regeneration

Axolotl is a salamander capable of self-healing, regrowth of injured limbs. Scientists are looking for ways to apply this to human regeneration.

Axolotl is a species of salamander being hunted by the world science world. The reason is its unique feature: Many lost parts can be reproduced.

According to the New York TimesAxolotl also has an unusual feature compared to other amphibians that do not undergo molting, change shape. They have a pale pink, yellow or gray, black appearance; Spotted body with a smiling face.

Today, this animal is in danger of being threatened by the environment and by human hunting. Axolotl survives only in the canals of Lake Xochimilco, the southernmost tip of Mexico.

The mystery of the genome of a self-regenerating animal

Researcher Randal Randal Voss, University of Kentucky, USA, said: “It is difficult to find things that they cannot replicate: From limbs, tail, spinal cord, eyes, even the retina in some “We have also seen the process of regenerating half of their brains.”

Thanks to this feature, the genome of Axolotl has become something of interest to the scientific community. Recently, in an upcoming article to be published in the Proceedings of the National Academy of Sciences (PNAS) on April 13, geneticists have a clearer view of the salamanders genome. This is on the chromosome scale, in the folded form. The study was chaired by the authors at the Vienna Center for Biology, BioCenter Institute for Molecular Pathology, Austria.

The study looks at how the genome of Axolotl folds inside at the molecular level and the position of the DNA sequences that regulate the genes involved in the regeneration and healing of cells. When fully stretched, each human DNA strand is longer than 1.8 m. However, Axolotl’s DNA strand is more than 9.1 m long.

A wild Axolotl in a conservation laboratory in Mexico in 2014. Photo: AFP.

“This work has arranged the DNA fragments in the Axolotl genome in the right order, as if it were on a chromosome. This is very important because in all vertebrates, genes are turned on and off with a controlled sequence located quite far from them, ”says biochemist Elly Tanaka, Vienna Institute of Molecular Pathology, BioCenter. about Axolotl but not participating in this project, reviews.

She also said that the study of the authors at the BioCenter Molecular Pathology Institute is very important because it will answer the question of whether the regeneration mechanism in Axolotl can be activated in humans.

After regenerating the entire gene in the folded form of Axolotl, the authors expect to simulate it in 3D in the future.

Two mysterious genes of Axolotl

According to Professor, Dr. Parker Flowers, Craig Crews Laboratory, Yale University, USA, Axolotl regenerates, self-healing most organs and organs after any injury. Therefore, it is difficult to have any injuries to kill this salamander.

If scientists find the genetic basis for the regenerative ability of Axolotl, they may discover something unprecedented. It is a way of restoring damaged tissues in humans.

But that job is not easy. Because the characteristics of the species Axolotl are not like humans. They have a larger genome than any other animal that humans have ever sequenced. This genome is even 10 times larger than the entire human genome.

At the end of January 2020, Professor Parker and his colleagues in the magazine post eLife revealed they have found the key to these problems. The authors found a way to disrupt the complex genome of the salamander Axolotl and identify at least two genes involved in post-traumatic body regeneration.

According to the Science Daily, the advent of next-generation gene-editing and sequencing technologies has allowed researchers to list hundreds of gene candidates that can reproduce the extremities. However, the giant size of the Axolotl genome produces repetitive DNA fragments, making it difficult to dissect and analyze them.

Researcher Lucas Sanor, co-author of the Craig Crews lab project, used multi-step gene editing to record baseline markers, tracking 25 genes believed to be involved in the regeneration process. Genus in Axolotl. Thanks to that, they identified two genes in blastema dividing cells responsible for regenerating part of their tail when injured or severed.

But that’s not all. Professor Parker emphasized that Axolotl’s body still has many similar genes. And humans have similar DNA with Axolotl so scientists can discover how to activate tissue, cells speed up wound repair, regenerate lost parts.

Axolotl salamander has a pale pink, yellow or gray, black appearance, and a smiling face. Photo: Getty Images.

Decoding the entire gene of Axolotl for the first time

Before the study of Professor Parker Flowers and colleagues, at the end of November 2018, the group of authors at the University of Kentucky, USA, published the most complete simulation of Axolotl’s DNA. Research published in the journal Genome Research, is considered to pave the way for transformations in human regenerative medicine.

Many animals are able to perform some degree of regeneration and self-healing. However, Axolotl is the only species that is nearly limitless in terms of this ability. Associate Professor, Dr. Jeramiah Smith, University of Kentucky and colleagues decided to find answers about the healing superpower of Axolotl through sequencing all genes.

Based on previous research, the authors have mapped more than 100,000 pieces of DNA onto chromosomes, the genetic makeup in the nucleus of each cell. The Axolotl genome is the largest product assembled at this level.

The authors used a design mapping method, which relies on the fact that the strands of DNA are physically close together on one chromosome and tend to move together. To determine the specific DNA of Axolotl, they grafted Axolotl with the tiger salamander – a close relative. They were then mated back to generation F1 with purebred Axolotl.

The process of regeneration of the extremities of Axolotl salamander. Photo: eLife.

Tracking genotypes on 48 out of all F2, they were able to deduce which DNA sequences belong to the Axolots and where they are located in the 14 chromosomes of amphibians. During the study, the authors identified a genetic mutation that causes heart defects in Axolotl.

“Just a few years ago, no one thought it was possible to decode genomes with more than 30 GB capacity. Now, we have many methods to approach and open up the ability to decode large genomic animals more often, “says biological researcher Jeramiah Smith.

The team also hopes that understanding the axolotl’s post-sequencing genome will help in future medicine. “Now we can go into the genome sequence, find out what makes this salamander strange. Hopefully one day, we can make the collected information useful for human therapy, the potentials that may not be fully exploited of each part of the body ”, Mr. Voss identify.