Four key transcription factors associated with skin healing.

There's a classic episode in "Superman", in which Superman masquerades as the mortal Clark Kent, and after being burned, the burnwound wound heals instantly, almost letting his friend know that he is Superman.
scratched a small wound, skin healing is common, but if the wound is too large, instant repair becomes super-powerful.
, Nature published a study by scientists in the United States and other countries that unearthed the "super-power" of skin healing: a viral vector that transfers specific transcription factors (a regulatory gene) into mouse vent cells and finds that wounds that could not be healed heal quickly.
researchers spent a lot of time "choosing" which transcription factors were associated with healing, and after multiple rounds of screening, identified four key transcription factors that converted ordinary skin cells into a "keratito-forming cell" that led to a "new life" in the skin.
ordinary cells with the use of transcription factor bath fire rebirth as the body's largest protective organ, the appearance of the skin looks like a wall, but the wall is inside the surging, different types of cells migrate between different layers, for example, formation cells from the adjacent epidermis to the wound to promote reskining, into a new force to repair damaged skin.
class of cells, known as "keratin-forming cells," are the "bricks" that are new, where the trauma moves.
these "extraordinary" cells in the skin cell population can promote skin rebirth, so that the "ordinary" cells at the wound can be converted into "extraordinary" cells, can it solve the problem? The difference between "extraordinary" and "ordinary" is determined by the expression of genes within the cell.
for this purpose, the team compared the gene expression spectrum between the horny-forming cells and the human skin fibroblasts.
use RNA sequencing and other techniques to analyze what differences the two cells differ in gene expression.
" the genetic expression differences between the two cells are very large. huang Pengyu, a researcher at the School of Life Sciences and Technology at Shanghai University of Science and Technology, explained
, that thousands of genes can be found to differ in expression.
the research team focused on the different expression of transcription factors, "transcriptiating factors are a kind of regulatory gene, often regulating the expression of hundreds of functional genes, and thus determine the 'destiny' of cells."
," Huang Pengyu said.
the paper shows that, using "ordinary" cells as a comparison, the team identified 55 transcription factors and 31 tiny RNA in a large number of different "extraordinary" cells based on the expression analysis, upstream initiator analysis and other factors, and their expression differences in the two cells are very significant, which probably includes the cell as the determining factor for keratin formation cells.
"sea selection" followed by "qualifying."
for clinical applications, 86 factors are too many, the primary screening factor narrows the scope of the application is possible.
" the method chosen for the study is innovative.
Huang Pengyu explained that they transferred all the factors together into skin cells to see the results, those who survived, turned into formation cells, jumped out.
this is a rough, gladiatorial qualifying match.
"ordinary" cells and slow virus vectors with different genes meet, randomly "eat" the virus vector into the genome, cell life activities will experience "storm" level vibration, "cells in the process will occur a variety of changes, and even death."
," Huang Pengyu said.
", "There is a great risk of this screening method, one is whether there will be cells to survive, the other is to analyze these cells to determine 28 factors, the relevant experimental techniques may have false negative phenomenon."
" Huang Pengyu said, which is also the reason why such research and exploration often have no breakthrough over the years, the need to "sit on the cold bench" of perseverance and spirit.
a small number of "ordinary" cells with the help of the power of foreign transcription factors "bath fire rebirth", experienced into a fresh epithelial cell can become an teratomatic formation cell.
the "minus one" method and found four "superfactors" in "reborn" cells, and the team found that 28 transcription factors were "eaten" into the genome sinofa.
"28 transcription factors are still too many, and the team used the 'minus one' method for further screening.
" Huang Pengyu said, the aim is to focus on which factors are indispensable and which are available.
strict "minus one" approach means an unimaginable amount of work.
Huang Pengyu for example, 28 factors, in turn to reduce one, plus the control group in the first round to do 29 sets of conversion, the second round to do 28 ... And so on, each conversion will take 4-5 weeks to complete, and two dozen rounds will take at least three years to complete.
" team should have conducted analysis during the experiment, adhered to some tendentious guidelines, and selectively validated the experiment.
" Huang Pengyu believes that this not only tests the level of scientific research, but also needs the luck component of scientific exploration.
lucky, 28 transcription factors were reduced to four in a relatively short period of time: DNP63A, GRHL2, TFAP2A and MYC (DGTM factor).
the final method used in the study is similar to that of the 2012 Nobel Laureate Yamanaka team, but has been targeted in screening ideas.
" results also partly reflect the team's innovative thinking.
" Huang Pengyu explained that, under normal circumstances, researchers would focus on screening "what is unique", that is, what is in the cell, but the four factors isolated at present are not all unique genes in these cells, but are highly expressed genes in many cells.
this also has a strong inspiration for the future development of other trans-differentiated technologies.
find a needle in a haystack, "super factor" is OK? The team made ulcers in mice and designed a wall that deftly prevented other formation cells from beating support.
on such an unhealable wound, when the skin ulcers in mice were treated locally with these four deterministic factors, healthy epithelial cells grew within 18 days, and the epithelial cells gradually expanded to allow large areas of ulcers to heal;
make "cell superman" on the clinic, but also a lot of work through the cell trans-differentiation technology to obtain new cells, human organ repair attempts have a long history - as early as 40 years ago, there are scholars try to express a transcription factor, so that fibroblasts into muscle cells;
"Not many are currently in clinical trials.
"Huang Pengyu introduction, trans-differentiation to obtain the "cell superman" need stoic to meet three basic requirements to be considered to have application prospects: First, the conversion efficiency is high enough, second, the function of the cells is good enough, and third, is safe enough not to have tumor-causing.
study, for example, the clinical obstacles it faces may be in terms of tumor-causing.
experimental results show that the trans-differentiation efficiency is about 0.1%, and can promote the healing of large areas of wounds, that is, can meet the first two conditions.
but in terms of tumor-causing, Huang Pengyu said: "Two genes in the DGTM factor are closely related to cell proliferation.
DNP63A and MYC are genes that promote tumor development.
the study, MYC appears likely to be culled, but further strategies need to be found to replace DNP63A before it can be clinically available, or to prove its safety with a large number of experiments.
", scientists are doing a lot of research on the regeneration of tissues with broad applications, such as nerve cells, liver cells, heart muscle cells, and skin cells.
China has also made a number of breakthrough achievements in this field, and has been in the "hepatic cell" aspect of the road from the laboratory to clinical trials.
related data show that the Chinese Academy of Sciences Shanghai Institute of Biochemistry and Cell Biology Researcher Hui Lijian team in the establishment of the skin fibroblasts induced into liver cells on the basis of cooperation with a number of units, breakthrough "hepatocellular- in vitro culture technology, successfully developed a biological artificial liver system, through the preparation of liver-like cells with detoxification function, "clean and nutrition" from the patient's body from the plasma, and then back into the body, treatment of acute liver failure patients.
has so far completed the treatment of about 10 patients.
"The technology was published in Nature in 2011 and won the 'Top Ten Advances in Science in China' that year."
will not be implemented until 2014.
is still not industrialization, in clinical trials and industrialization of the 'double push' stage. Huang Pengyu, who has been involved in the development of the technology at the
, said that after the relevant theories are clear, a lot of difficult optimization and improvement work is needed to move on to clinical trials and eventually to clinical applications.
Source: Science Daily.