1.Cell Rep: Scientists have found a chain reaction to protect breastcancer stem cells in chemotherapy
doi:10.1016/j.celrep.2017.02.001
By usinghuman breast cancer cells and mouse models, researchers from Johns HopkinsUniversity have discovered a new biochemical pathway that stimulates theregeneration of breast cancer stem cells after chemotherapy. Tumor stem cellregeneration is an important cause of resistance to chemotherapy in most breastand other cancer patients, which makes chemotherapy only effective in the shortterm, and tumor recurrence after chemotherapy is often fatal.
In a newstudy published in Cell Reports, Semenza and colleagues used a series oflaboratory-grown breast cancer cells that were treated with chemotherapeuticagents such as carboplatin that could damage cancer cell DNA, and they weregenetically expressed analysis. They found a higher level ofglutathione-S-transferase 01 (GST01) in surviving cancer cells. Experimentsshow that in the course of chemotherapy, HIFs control the production of GST01in breast cancer cells, if the inhibition of HIFs activity, cells can notproduce GST01.
Semenzanotes that GST01 and the associated GST protein are antioxidants, but thecancer resistance of cancer cells does not require GST01 to exert antioxidanteffects. Instead, GST01 binds to a protein called sorbitan receptor 1 (RYR1)during chemotherapy, which promotes the release of calcium ions, which in turncauses a chain reaction that converts breast cancer cells into breast cancerstem cells.
To further assess the role of GST01 and RYR1 in breastcancer response to chemotherapy, the researchers injected human breast cancercells into the mammary gland of mice and then treated with carboplatin aftertumor formation. In addition to using normal breast cancer cells, the researchersalso used breast cancer cells that were genetically engineered to lose GST01 orRYR1. The researchers found that breast cancer cells lacking GST01 or RYR1 hadfewer tumors in the tumor, and the ability of the tumor to metastasize from theprimary lesion to the lungs was reduced. At the same time, the time requiredfor chemotherapy to reduce the tumor was shorter. No time to regenerate thetumor.
2.BMC Medicine Obesity leadsto reprogramming of muscle stem cells
doi:10.1186/s12916-017-0792-x
Obesityis associated with decreased muscle mass and metabolic abnormalities. Accordingto a new study from the University of Delong, Sweden, epigenetic changes thataffect neovascularization may be one of the incentives.
In thisnew study, Dr. Cajsa Davegårdh studied DNA methylation in obese and normalindividual muscle stem cells. DNA methylation is an epigenetic process where DNAmethylation binds to the gene and regulates gene activity as well as a lightswitch. By comparing the methylation levels of immature and mature muscle stemcells, Cajsa Davegårdh found that actual methylation levels have an importanteffect on the maturation of muscle stem cells.
"Immaturemuscular stem cells have also altered the level of methylation of many genesthat have altered expression levels in the development of mature muscle stemcells, suggesting that methylation is associated with gene expression,"she explains. She found that an antipyretic factor called IL-32 is essentialfor maturation and insulin sensitivity. Insulin sensitivity abnormalities arecommon in obese patients and are a risk factor for type 2 diabetes."Decreasing the expression of the gene can increase muscle insulinsensitivity." These findings were also validated in mouse experiments.
Subsequently, Cajsa Davegårdh compared the differences inDNA methylation levels of muscle stem cells from normal and obese individuals(BMI greater than 30). She found that obese individuals and normal individualmuscle stem cells in the process of regulating the genes are different, and thedegree of methylation changes in the gene also has significant differences.
3.Cell Rep: ears are not heard?The future is expected to use drugs for treatment
doi:10.1016/j.celrep.2017.01.066
Eachperson has about 15,000 hair cells in each ear, and once the damage occurs,these cells do not grow again. Researchers from research institutions such asMIT have recently discovered that a combination of drugs can promote theexpansion of progenitor cells within the ear and induce them to form haircells, providing a new potential for the treatment of deafness. The results ofthe study were published in the International Academic Journal Cell Reports.
In aprevious study, the researchers had found that exposure of small intestinalstem cells to specific molecules could result in a large number of immaturesmall intestinal cells that could later stimulate further differentiation ofthese cells, and they also found that cells responsible for providingstructural support in the cochlea also expressed Small intestinal stem cellswith the same surface markers. So they decided to further explore whether thesame method was equally effective for supporting cells.
They willbe from the mouse cochlea cells in the laboratory and then activate the Wntsignaling pathway of some molecules to stimulate cells to promote rapid cellproliferation. At the same time, in order to prevent the rapid differentiationof proliferating cells, they also stimulate cells with molecules that activatethe Notch signaling pathway.
Afterobtaining a large number of immature progenitor cells, the researchers addedanother group of molecules to the cultured cells to promote cell differentiationinto mature hair cells. This method achieves higher efficiency of hair cellsthan in the previous best.
The researchers also found that their new method wasequally effective for removing the complete cochlea from the mice. In thisexperiment, the researchers did not need to add molecules that activate theNotch signaling pathway, because the progenitor cells, once formed, naturallyform mature hair cells.
4.heavy! Nat Methods issueda report on how to predict the development of hematopoietic stem cells
doi:10.1038/nmeth.4182
Depthlearning has attracted more and more attention, such as automatic driving,automatic voice recognition and so on. Researchers from the German Center forEnvironmental Health Research, the Zurich Federal Institute of Technology andthe University of Munich (TUM) have recently used depth studies to determinethe direction of hematopoietic stem cell development. In this article,published in Nature Methods, they describe how they use their software topredict the future types of hematopoietic stem cells based on microscopicimaging.
Today,Carsten Marr and his team have developed a new algorithm that predicts thedirection of hematopoietic stem cells in advance. The so-called depth oflearning is the key to this approach. "The depth of the neural networkplays an important role in our approach," Marr said. "Our algorithmclassifies these cells by learning the experimental data on the development ofsuch cells in the past using optical imaging images and video of individualcells. The way the algorithm will learn how cells divide. "
Researchers have examined the hematopoietic stem cellimages taken by the Timm Schroeder laboratory microscope at the FederalInstitute of Technology in Zurich. Through the shape and velocity information,the software can remember the corresponding behavior patterns and predict them."Compared with the traditional method, we can know the direction of celldifferentiation 3 generations ahead of time."
5.JAMA Neurol: Stem CellTransplantation or Treatment of Multiple Sclerosis But How To Choose a PatientIs Important
doi:10.1001/jamaneurol.2016.5867
A newstudy shows that stem cell transplantation or can delay about half of patientswith multiple sclerosis disease progression, but the selection of appropriatepatients is the key to successful treatment. Researchers have found that youngpatients with relapsing multiple sclerosis but who have not experienced severeinconvenience and have no remission from other treatments will achieve betterresults within five years. But the researchers also reported that stem celltransplantation could cause some patients to die.
In orderto understand how long the patient was after prolonged exposure to stem celltransplantation, the researchers conducted a follow-up analysis of 281 patientswho received stem cell transplantation from 1995 to 2006. They found that 46%of patients did not develop disease within five years of transplantation.However, eight patients (nearly 3%) died within 100 days of transplantation,and their death was associated with transplantation.
Researchers believe that these deaths may be mainly relatedto the technique of stem cell transplantation before 2006, which has beenimproved later.
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