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News Gene regulator that controls hemogenic endothelium

Article in 'News' Written by Arul Prakash Published Dec 3, 2013

  1. Researchers have found a key regulator that controls the production of early blood stem cells and adult blood system from hemogenic endothelial cells.

    The study done by Wisconsin Institutes for Medical Research and UW-Madison Blood Research Program revealed how a protein called RUNX-1 allows the hemogenic endothelial cells which line the walls of major human blood vessel dorsal aorta to produce adult blood stem cells, the same stem cells responsible for the production of our blood.
    A close up of the cellular budding (green). The clusters of hematopoietic stem cells emerging from the special cells that line the dorsal aorta (magenta). The image was produced by Xin Gao using confocal microscopy.
    The actual control of production of stem cells begins when a tiny sequence (+9.5) of GATA-2 gene activates GATA-2 protein when in turn activates RUNX1 and other regulatory factors in the hemogenic endothelial cells.

    Researchers were able to stop the production of blood stem cells within 10 days in embryonic mice by deleting the specific sequence (+9.5) of GATA-2 gene but proved fatal in 14 days. The team points out that this domino effect of downstream cell signalling can be halted by reintroducing GATA-2 or RUNX-1.

    3D view of the cluster
    However, Bresnick points out that since “GATA-2 regulates multiple genes required for the stem cell production, one needs to consider how the overall genetic network mediates this critical process, and we are making significant strides in understanding the problem at this level.”

    Diseases like leukemia occur due to improper production of blood stem cells.

    “The +9.5 site is essential to generate the stem cells that form adult blood cells,” said Bresnick, who is also the director of the UW Blood Research Program. “When this region is corrupted later in life, GATA-2 expression drops, yielding an immunodeficiency as a child or adult. The immunodeficiency commonly progresses to myelodysplastic syndrome and acute myeloid leukemia. Gaining a clear mechanistic insight into how this process is regulated will almost certainly provide new opportunities for targeting blood cancers."
    • Arul Prakash

      Article by Arul Prakash

      Editor and founder of BiotechCareer.Org. He is an Industrial Biotechnologists and also a web developer, gooner, blogger, and foodie.

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