In August 2009, Xiao Haruko began to write the first paper on STAP cells, and submitted it to the scientific magazine Nature in the spring of 20 10. However, it is common knowledge in the field of cytology that "animal cells cannot obtain pluripotency by receiving external stimuli", and this paper failed. Hiroshi Kojima, an associate professor at Harvard University who works in the laboratory of Professor Charles Vacanti and her co-author, commented that "in the next 2-3 years, she (Haruko Bao Fang Jr.) was really miserable".
20 1 1 In March, Wakayama Akihiko, director of the research team of Japanese Institute of Physical Chemistry (later professor of Yamanashi University), offered to lend a helping hand, so Bao Fang Haruko Jr. joined the research team of Akihiko of Wakayama and became a visiting researcher of the Institute of Physical Chemistry.
Studies have shown that the transformation of cell types can be achieved through "cell reprogramming"-by introducing certain transcription factors under certain conditions, researchers can change the degree of cell specialization. In 2006, Japanese team shinya yamanaka obtained induced pluripotent stem cells (iPSCs) by regulating four transcription factors, and was awarded the 20 12 Nobel Prize in Physiology. In 20 13, the research team led by Professor Deng Hongkui and Dr. Zhao Yang from Peking University College of Life Sciences discovered chemically induced pluripotent stem cells (IPSCs), and the global stem cell research began to enter a new era.
Haruko Bao Fang Jr. and his colleagues monitored the pluripotency of cells through fluorescent proteins. If the target cells show gene expression related to pluripotency, they can detect green fluorescence. The researchers tested white blood cells under different environmental pressures and found that some white blood cells exposed to low pH solutions activated pluripotent labels for a short time. The researchers collected these cells and found that they have the genetic marker of early embryos-the so-called "stimulus triggered pluripotent acquisition" (STAP).
At first, the research team tried to find STAP cells through acid solution stimulation, but all failed, but they did not give up and continued to try stimulation methods. Finally, at the end of 20 1 1, they found a bright spot of pluripotent cells marked with green fluorescence from stimulated experimental mice.
After that, the research team soaked the lymphocytes of the newly born experimental mice in a weak acidic solution for about 30 minutes and cultured them, and obtained the result that the genes with the ability to evolve into various cells for a long time were activated. The researchers put the cells into experimental mice and confirmed that they evolved into various cells such as skin and muscle.
2065438+200465438+1October 29th, Japan Institute of Physical Chemistry held a press conference, claiming that Xiao Haruko's research team had successfully discovered the research results of STAP cells, a new universal cell similar to iPS cells. This achievement was published in the journal Nature in the form of papers and letters (No.505, No.641–647 and No.676–680, No.2014, No.65438+1October 30th). The first author of the two papers is Haruko Kobayashi, and the correspondent is Charles Vicati. Professor Akihiko from Wakayama and colleagues Yoshiki Hayashi Sakai and Dan Shiren from the Institute of Physical and Chemical Research are also co-authors of these two papers.
The first paper mainly reports the discovery of STAP (stimulus-triggered pluripotent acquisition), that is, a sublethal external stimulus, such as weak acid environment, can reprogram mammalian somatic cells into pluripotent cells, and reports how to isolate an expandable pluripotent cell line from STAP cells. The second paper focuses on the report that pluripotent cells obtained by STAP can form chimeras with embryonic stem cells (es), which is helpful for the development of embryos and placentas.
All along, "universal cells" are represented by iPS cells, which are made by introducing genetic genes into cells such as skin. The newly born universal cells can be generated in a short time by external stimulation, which is a relatively simple method, so it has attracted the attention of all parties.
According to Haruko Bao Fang Jr., unlike iPS cells and other technologies, the highlight of this innovative technology is that cells can be changed simply by changing the external environment and giving them stimulation. At the same time, she also believes that this technology should contribute to the field of regenerative medicine and immune research. The research team decided to continue the research to find out whether this new technology can also be applied to human cells.
The publication of these two papers immediately caused a sensation. Chris Mason, a professor at the University of London in the United Kingdom, commented that this is an important rewriting of the method of making universal cells by Japanese scientists. Shinya yamanaka used four genes to control the production of artificial pluripotent stem cells (iPS cells), and STAP cells can be cultured in acidic solution. The method is simpler; Differentiated cells can be reprogrammed into embryonic-like state by physical stimulation, and the method proposed by Kohokata et al. is described by a simple program. At this time, shinya yamanaka is already the director of iPS Cell Research Institute of Kyoto University. As a young Japanese scholar, he is very proud of his discovery. STAP cells may also break through the bottleneck that iPS cells are difficult to regenerate in internal organs.
At the same time, the abstract of Kohokata's paper also emphasizes that the process of reprogramming requires neither nuclear transplantation nor genetic manipulation. The concepts of nuclear transplantation and gene manipulation are the reasons why Nobel Prize winners john gordon and shinya yamanaka won the Nobel Prize for 20 12 years respectively.