Highlights of science journals in November 2019

November 30, 2019 / BIOON / -- November 2019 is coming to an end What are the highlights of Science Journal in November worth learning? Xiaobian has sorted this out and shared it with you 1 Scientists in China have published two science papers to reveal the mystery of primate embryo development Doi: 10.1126/science.aax7890; doi: 10.1126/science.aaw5754; doi: 10.1126/science.aaz6976 gastrulation is a milestone event in development, which involves a series of complex molecular, physical and energy remodeling changes in early embryogenesis This process of transformation is different among different species, which leads to the diversity of animal forms on the earth Due to technical and ethical limitations, the molecular and cellular mechanisms of progut embryogenesis in primates are unclear The lack of samples of primate embryos at the gastrulation stage limits scientists' understanding of this critical event in primates Recently, human embryos have been cultured in vitro for 12 to 13 days Many governments and international organizations suggest that human embryos should not be cultured in vitro for more than 14 days Therefore, it is reasonable to expect that the analysis of non-human primate embryo model system will clarify the mechanism of projejunal embryo formation, and it is expected to clarify how human development and early development process abnormalities lead to development defects and diseases Monkeys have long been regarded as a reliable animal model for studying human physiological and pathological events, because they are highly similar to human in terms of genome and morphological characteristics In two new studies, Chinese researchers have developed an in vitro culture (IVC) system to study the development of cynomolgus monkey embryos after implantation to the gastrulation stage and beyond the gastrulation stage (9-20 days after fertilization) The relevant research results were published in the Science Journal on November 15, 2019, with the titles of "in vitro culture of sinomolgus monkey embaryos beyond early construction" and "dividing price early post impact development using long term in vitro embaryo culture" Monkey embryos are cultured in vivo more than in gastrulation stage The picture is from science, 2019, DOI: 10.1126/science.aax7890 In the first study, researchers from the Chinese Academy of Sciences developed a system to support the in vitro culture of cynomolgus monkey embryos for up to 20 days after fertilization By combining histological and immunofluorescence staining with single cell RNA sequencing (RNA SEQ) analysis, they found that the development of these in vitro cultured monkey embryos exceeded the early gastrulation stage, and summarized the key events of early development of primate embryos after implantation In the second study, researchers from Kunming University of science and technology, Shenzhen Huada Gene Research Institute, Chinese Academy of Sciences and other research institutions developed an in vitro culture system, which can study the growth process of primate embryos in the laboratory, and also help researchers to observe the molecular details of the key development process of embryos for the first time This research is carried out in non-human primate cells, which is also of great significance for the study of human early development; it can provide information on early embryonic development, and provide key information to improve the research progress of human regenerative medicine All in all, these two studies established an in vitro culture system, which can support the development of cynomolgus monkey embryos in vitro beyond the early gastrulation stage These IVC embryos outline many key events in the early development of primate embryos in vivo after implantation This monkey culture system provides a platform for the study of the specific molecular characteristics and mechanisms of early embryogenesis primates in the future These molecular characteristics and mechanisms may be related to the early development of human diseases 2 Science: Chinese and American scientists work together to reveal the mechanism of action of RSC complex from the structure, which is helpful to generate new insights for cancer Doi: 10.1126/science.aay0033 cell machine controlling chromosome structure, such as RSC complex, has mutation in about one fifth of human cancers Now, in a new study, researchers from Tsinghua University in China, Peking University and the University of Utah Medical School in the United States have for the first time constructed a high-resolution visual map of RSC complex, illustrating the working principle of this multi protein machine and its role in healthy cells and cancer cells The corresponding authors of the paper are Dr Zhucheng Chen, associate professor of Life Science College of Tsinghua University, Dr Ning Gao, Professor of Life Science College of Peking University, and Dr Bradley Cairns, cancer researcher of Huntsman Cancer Institute, medical school of Utah University The relevant research results were published online in the journal Science on October 31, 2019, with the title of "structure of the RSC complex bound to the nucleus" Gene expression is the basis of every cell behavior in all living organisms Gene expression provides a blueprint for cells to coordinate their actions, including growth, death, and response to changes in their environment Gene expression is essential for living healthy cells and cancer cells However, cancer cells express genes with defective instructions, which often lead to uncontrolled growth RSC and its related complexes are key regulators of chromosome structure and gene expression Once the RSC complex binds to the genome, it will perform a machine like motion, exposing DNA fragments in the chromosome, thus triggering gene expression The researchers determined how the complex works with chromosomes These findings will provide important new insights into the way certain cancers are produced Since RSC complex plays an important role in both healthy and cancer cells, now they can accurately visualize the high-resolution image of RSC complex, including all its components They were able to see how the complex interacts with chromosomes and DNA and how it moves This provides vital information to understand how RSC like compounds are involved in the development of cancer 3 Science: activation of ISR switch is expected to treat Down syndrome Doi: 10.1126/science.aaw5185; doi: 10.1126/science.aaz7128 Down syndrome is the most common genetic cause of mental disorders Currently, there is no effective treatment Memory impairment is a typical feature of this disease In a new study, researchers from Baylor Medical College and other research institutions reported that a defect in the conservative stress pathway called integrated stress response (ISR) may explain the cognitive defect in Down's syndrome mouse model The relevant research results were published in the Science Journal on November 15, 2019, and the title of the paper is "activation of the ISR medites the behavioral and neurological abnormalities in Down syndrome" The authors found that ISR was activated in the brains of mice that reproduced cognitive impairment in patients with Down's syndrome, and also in human brain samples after death What's more, whether it is through genetic means or drug means to inhibit ISR, these mice can reverse the memory deficit These findings support future studies to explore whether regulation of ISR may contribute to the treatment of Down's syndrome and other diseases caused by disruption of the ISR pathway 4 Science: PIK3CA double mutation makes breast cancer patients more sensitive to PI3K inhibitor doi: 10.1126/science.aaw9032; doi: 10.1126/science.aaz4016 in a new study, researchers from multiple research institutions in the United States found that a subpopulation of breast cancer contains two PIK3CA mutations, and the two mutations occur on the same allele of PIK3CA The relevant research results were published in the Science Journal on November 8, 2019, and the title of the paper is "double PIK3CA residences in cis increaseoncogenicity and sensitivity to PI3K α investors" In this paper, they describe their work on the PIK3CA gene and its role in the production of human cancer Alex Toker of Harvard Medical School in the United States published an article of opinion type on the same issue of Science Journal, outlining their research work and its possible impact The picture is from cc0 public domain PIK3CA is a cancer gene and one of the most common mutations in human cancer Under normal circumstances, it is this gene that correctly encodes protein p110a Growth factors activate receptor tyrosine kinase, which leads to the recruitment of PI3K pathway This leads to the conversion of phosphatidylinositol 4,5 diphosphate (PIP2) to phosphatidylinositol triphosphate (PIP3) (PIP2 and PIP3 are two components of cell membrane) PIP3 then recruits downstream effectors, one of which is Akt pathway, which stimulates the growth of healthy cells In cancer cases, mutations in PIK3CA lead to over activation of the Akt pathway, which means that more Akt will be produced, leading to over stimulation of cell growth and subsequent tumor production In this new study, the researchers found that sometimes there are multiple mutations in PIK3CA, and these mutations occur in the same allele, the result is to promote tumor growth More specifically, they found that double mutations in PIK3CA occur in about 8% to 12% of breast cancer patients (both primary and metastatic) 5 Science: full text interpretation! To reveal the mechanism of Pax3 mRNA controlling the fate of muscle stem cells: doi: 10.1126/science.aax1694; doi: 10.1126/science.aaz4859 tissue homeostasis and regeneration depend on the tissue-specific stem cell population, some of which remain in a static state for a long time In vertebrates, muscle stem cells (musc) are necessary for skeletal muscle regeneration Recent studies have shown that musc in sedentary immobile mice plays an important role in the maintenance of adult muscle fibers They contribute more to the diaphragm muscle, but less to the lower hindlimb muscle In a new study, in order to understand the mechanism of determining the contribution of musc to adult muscle fibers, Thomas rando of Stanford University School of medicine and his team measured the degree of activation of musc into cell cycle in different intact muscles When mice were stimulated in vivo with 5-ethynyl-2 '- deoxyuridine (EDU), a nucleotide analogue, to label cells undergoing DNA replication, they observed extensive incorporation of edu Diaphragm, gracilis and triceps muscles showed the highest number of muscs They spontaneously broke the static state and entered the cell cycle under steady-state conditions, while hindlimb muscles showed the lowest number of muscs Musc in diaphragm, gracilis and triceps expressed Pax3 at a high level, while musc in limb muscle did not Given the established role of Pax3 in promoting cell proliferation and coping with stress during embryogenesis, these researchers studied whether Pax3 regulates the activation of musc during homeostasis They observed a positive correlation between Pax3 and edu incorporation in muscs from different muscles In order to directly test whether Pax3 is in balance between the static and active of musc