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A chronic lack of Phf19 can lead to abnormal hemagic function, pictured from Science Advances, 2020, doi:10.1126/sciadv.abb2745.
blood is a complex tissue of different specific cells (white blood cells, red blood cells, plate plates, etc.) that perform basic functions such as transporting oxygen and nutrients, maintaining body temperature, or regulating the immune system.
blood cells are produced by preaccumular cells stored in the bone --- cells --- HSC.
affects the majority of the world's population.
one in four people has anemia, 17 out of every 100,000 have haemophilia and 2.5 out of 100 tumours found worldwide are leukemia.
all these abnormalities are caused by abnormal blood cell function or an imbalance in the composition of blood tissue.
to maintain the balance of blood tissue is complex because each cell has a different life span.
life span of white blood cells is 5 to 20 days, while the life span of red blood cells is 120 days.
in the face of threats such as wounds or bleeding, in order to update these types of cells, HSC, which usually remains dormant, begins to divide and produce specialized cells to maintain the balance of blood tissue.
the transition from HSC to specialized cells is regulated by the observational genetic regulator--- which genes are expressed at each time and in each cell tissue---
, a team led by paper co-author Luciano Di Croce studied the Phf19 gene, part of a large group of surface genetic regulators.
, "The bone marrow cells continue to divide and are very sensitive to environmental factors such as radiotherapy or chemotherapy," explains Arantxa Gutiérrez, co-author of the paper.
because of the plasticity of HSC, any changes that affect gene expression in these cells, including the on-the-look genetic regulator, can have a significant impact on blood balance.
new study, the authors describe the role of the overt genetic regulator Phf19 in maintaining HSC.
genetically modified mice to remove the Phf19 gene without affecting their normal lifespan.
the absence of this gene, the area of the mouse genome containing the genes responsible for HSC differentiation is more compact, and these genes are not expressed.
, HSC remains stationary and does not differentiate much into specialized cells.
authors found that under normal circumstances, life in mice is healthy, but in some cases, such as transplantation or aging, it is difficult to produce specialized cells, which affects the normal functioning of blood tissue.
long term, animals lacking Phf19 accumulate blood composition disorders that are appropriate for the early stages of leukemia.
most of the studies done so far have removed all biogenic functions of Ppfh19 as part of a polyprotein complex," explains Di Croce.
we took a more subtle approach, by eliminating a single gene, to find that it played an unexpected role in the regulation of MHC.
Previously, aging was known to regulate the amount and activity of PHF19 proteins and other proteins in the protein complex in which it is located, both in mice and in humans," Di Croce said.
" before, however, it was not known that PHF19 controlled HSC activation to begin producing specialized cells.
Infesting stem cells to regulate genetic information to produce specialized cells is critical to understanding how cells achieve pluripotentity and proliferation ---three are also key features of tumor formation--- according to co-lead author ---.
lack of Phf19 increases the likelihood of blood disorders.
that's why we're looking at the role it may play in tumor prebiotic formation, or whether it could be a target for cancer treatment.
" Reference: 1. Pedro Vizán et al. The Polycomb-associated factor PHF19 controls hematopotic stem cell state and profile. Science Advances, 2020, doi:10.1126/sciadv.abb2745. 2.Epigenetics key to daily production of 10 billion blood cells without mistakes.