Mount Sinai School of Medicine cracks the mechanism of genomic integrity to protect the ability of embryonic stem cells to renew autonomously.

The kinases and phosphatases that regulate phosphorylation are important molecules for coordinating multi-pathway signaling, but the research on phosphorylation regulatory molecules in the field of stem cells is very limited.
August 6, 2019, Dr. Dongfang Li and Dr. Su Jie of Mount Sinai School of Medicine in New York, USA, published an article on Cell Reports, Genomic Integrity Safeguards Self-Renewal in Stem Cells, using functional genome screening to design a phosphorylation regulatory molecular gene silencing (shRNA) screening library containing 104 stem cells, using an unbiased screening and multicellular line verification method. Chek1, Ppm1g, Ppp2r1b and Aurka.
by analyzing the effects of these five molecules on the whole genome, the authors found that lowering the five molecules would weaken the ability of stem cells to renew autonomously and related genes, and lead to stem cells to differentiate in the direction of the mid-embryo and outer embryo layers.
interesting, all five molecules are associated with maintaining genomic integrity, and lowering the five molecules activates the genes associated with DNA damage repair and the downstream genes of p53.
at the same time, lowering p53 would weaken the effects of knocking down the five molecules on the autorenewal of stem cells.
the evidence shows the important role of the stability and integrity of the genome in maintaining the ability of stem cells to renew themselves.
the authors further used two drugs that could cause DNA replication damage, hydroxyurea and aphidicolin. both drugs
can differentiate stem cells and lose the ability to renew themselves autonomously.
, by knocking down a range of genes associated with DNA replication damage, DNA replication checkpoints, mRNA processing, Fanconi anemia, and Charcot-Marie-Tooth disease, the authors found that lowering most of the genes in these genes affected stem cell autonomic renewal of pluripotentity and gene expression.
, the authors identified five important phosphorylation regulatory molecules by means of functional genome screening and systematic biological analysis, and revealed the important role of genome stability and integrity in the auto-renewal of stem cell energy through their common attributes to maintain genome integrity.
this paper began with a team led by Dr. Ihor Lemischka of Mount Sinai School of Medicine in New York, and was later completed by Dr. Su Jie at the Memorial Catherine Cancer Medical Center in New York and Dr. Li Dongfang at the Texas Medical School in Houston.
the death of Dr. Ihor Lemischka in 2017 in honor of his teachings to all the authors, and his passion and contribution to stem cell research has inspired and inspired the younger generation of researchers.
research background embryonic stem cells have the ability to independently renew and differentiate into various tissue cells in the body, which enables stem cells to provide a sustainable source of cells for clinical treatments such as organ transplantation.
coordination between various signaling pathways is very important to maintain the ability of embryonic stem cells to renew independently, but it is still not clear how stem cells maintain the specific cell mechanism of auto-renewal, and it is very important for basic scientific research and translational medicine research to study and maintain the molecular mechanism of stem cell auto-renewal.
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