Tsinghua's "magic potion" is published in nature: reversing stem cell differentiation, and the achievements of the Nobel Prize go further. Netizen: life can be created without sperm and eggs

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Create life without germ cells , It has always been one of the goals pursued by biology .

Now? , Tsinghua University has made a breakthrough in this field Nature：

The team first discovered a “ Magic potion ”, Can reprogram mouse cells into a kind of Totipotent stem cells .

Totipotent stem cells have unlimited differentiation potential , Any kind of organ or tissue cell can be cultivated .

That is, it can form life independently without sperm and eggs .

The school of pharmacy of Tsinghua University evaluated this achievement as “ It marks a new research field of life creation ”.

Sifted through thousands of chemicals 3 Kind of

To understand the breakthrough of this research , We need to know about stem cells first .

Totipotent stem cells  （totipotent stem cell） Such as fertilized eggs and undifferentiated embryos , Can be seen as the starting point of life , Have unlimited differentiation potential , It can differentiate into all tissues and organs .

Once totipotent stem cells continue to differentiate , You will lose part of your potential and become Pluripotent stem cells  （pluripotent stem cell）, Unable to develop into a complete individual .

Pluripotent stem cells can become Specialized stem cells  （multipotent stem cell）, Until they differentiate into various tissues and organ cells , Lose the ability to continue differentiation .

2006 year , Japanese scholars In the mountains Reverse mouse skin cells into pluripotent stem cells , And therefore get 2012 Nobel Prize in .

This achievement belongs to 0 To 1 Breakthrough , But there are still two problems , It limits the transformation from research to application .

One is that pluripotent stem cells have only partial potential , Unable to develop into a complete biological individual like a totipotent stem cell .

The other is early use Gene reprogramming technology , It is through viral vectors that 4 Three transcription factors were transferred into mouse cells .

But it was soon discovered that , Viral vectors integrate foreign genes into the host genome , There is a high risk of cancer .

After Nobuyasu Yamanaka , More secure Chemical reprogramming Technology is considered to have more clinical value .

The Tsinghua team conducted this research , It was the first chemical reprogramming , use Small molecule The drug combination induced the formation of Totipotent stem cells .

They lasted 6 year , Sifted through thousands of chemicals 3 A small molecule reagent ：TTNPB、1-Azakenpaullone and WS6.

These three drugs are synthesized according to their initials “ Artifact potion ” Name it “TAW Cocktail ”.

All three drugs alone can regulate the fate of specific cells , Such as TTNPB It is a retinoic acid receptor agonist ,1-Azakenpaullone Glycogen synthase kinase -3β Inhibitors of ,WS6 It is β Cell inducing proliferators .

But it is the first time that the combination of three drugs can induce the combined action of totipotent stem cells .

The team is right TAW The induced cells were in the transcriptome 、 Rigorous tests were performed at the level of the apparent group and the metabolome , It is confirmed that it is related to mice 2 Cells are similar to cells in the embryonic stage .

Hundreds of the genes that are common in totipotent stem cells are turned on , At the same time, the genes related to pluripotent stem cells are TAW The induced cells are silent .

Will be TAW The induced cells were injected into early mouse embryos , It has also been verified that it can differentiate into intraembryonic and extraembryonic lineages in vivo , Having the ability to develop into a fetus and yolk sac 、 The potential of the placenta .

Compared with , The pluripotent stem cells in the previous study can only develop into fetuses .

Besides ,TAW Induced cells can maintain totipotency in the laboratory environment , Achieve in vitro self replication , Make more scientific research on the origin of life possible .

The achievements come from the team of the first Dean of Tsinghua pharmaceutical college

This research was carried out by Professor Dingsheng and his team from the school of pharmacy of Tsinghua University .

among , Professor Dingsheng 、 Assistant researcher liukang 、 Associate researcher matianhua is the co corresponding author of this paper ; Huyanyan 、 Yang Yuanyuan 、 Tanpengcheng is the co-author of this article .

△  Picture source: School of pharmacy, Tsinghua University ： Group photo of main participants of Dingsheng team's research results

Tsinghua pharmaceutical college was established in 2015 year 12 month , Dingsheng was the first Dean .

He has... In the direction of inducing stem cells 20 Years of experience ——

He is in 1999 He received a bachelor's degree in chemistry from California Institute of technology , On 2003 He received a doctor's degree in chemistry from Scripps Institute .

And then , He worked at the Scripps Institute 、 Assistant professor at the University of California, San Francisco 、 Associate professor .

It is worth mentioning that , Professor Dingsheng also participated in the establishment of several biotechnology companies .

2022 year , Ding Sheng and Joe Betts-LaCroix and Matt Buckley Co founded Retro Biosciences Anti aging research company , still 4 Month got 1.8 Us $100 million financing .

Achievements in the field of stem cells have exploded

In recent years , Research in the field of stem cells is in the ascendant .

last year 9 month , Researchers at the University of Tokyo in Japan used mice Pluripotent stem cells , Reconstitute males in vitro Germ cells .

And then , The researchers successfully inseminated the female mice with the generated sperm , And gave birth to health 、 Fertile offspring .

The research results are presented in Cell Stem Cell Published in journals .

This year, 3 month , Chinese Academy of Sciences and Shenzhen Huada Institute of life sciences used genetic methods to induce “ Youngest ” Of human beings Totipotent stem cells .

Why are you the youngest ？

Because the research team used the culture medium to generate people 8 Embryonic like cells in cell stage （8CLC）, It is equivalent to the cleavage of the fertilized egg to about The first 3 God The state of ; And Shinya Yamanaka, who won the Nobel Prize before , Induced pluripotent stem cells , Equivalent to the development of fertilized eggs 5 to 6 God The state of .

The paper was published in Nature On .

Besides , Professor denghongkui of Peking University used Chemical reprogramming methods , Yes human beings Somatic reprogramming , Turn into Pluripotent stem cells .

Chemical reprogramming method in 13 It was first realized on mouse cells by the team in , after 9 After year , This method was finally applied to human cells , The research results are finally on the Nature.

The research results of Professor Dingsheng from Tsinghua University , use Chemical reprogramming methods It has realized the transformation of pluripotent stem cells to Totipotent stem cells The reversal of , Make new breakthroughs again .

at present , This paper is still in the accelerated preview status of the draft , After the final revision, it will be officially published .

Accelerated preview is Nature A tradition of , Every week, I will select several important papers to meet the readers in advance .

Sure enough, this paper has aroused the interest of scholars in related fields .

A scholar at the University of Texas Southwestern Medical Center is excited about the paper's achievement that totipotent stem cells can be obtained only by chemical methods . And verified one of their previous findings , But there are some criticisms for not quoting their articles .

A scholar from Edinburgh University believes that getting rid of the dependence on germ cells is a big thing .

But it seems that Japanese scholars are more concerned about this matter .

After all, except for the grandmaster, Nobuyasu Yamanaka , In the field of stem cells, there was also a little baofangqingzi who was implicated in his tutor's suicide due to academic fraud .

Address of thesis ：
https://www.nature.com/articles/s41586-022-04967-9
Reference link ：
[1]https://mp.weixin.qq.com/s/KuwpE9U5hSYV3Njh1vajQA
[2]https://mp.weixin.qq.com/s/15PKs727lo5TS2Jt4I-r5g
[3]https://www.technologynetworks.com/cell-science/articles/cell-potency-totipotent-vs-pluripotent-vs-multipotent-stem-cells-303218