Researchers find genes controlling bone marrow function


Bone marrow is the spongy tissue inside some bones containing immature cells that are capable of developing into blood cells to help the body battle infection or carry oxygen. It’s saved a vast number of lives over the years, but remains poorly understood at the genetic level.

Now, however, researchers from the University of Southern California (USC) have discovered a new group of genes that affects the development and maintenance of bone marrow (which is also known as blood stem cells). Their findings were published in the June edition of the journal Stem Cell Reports and could improve our understanding of how bone marrow functions.

As part of their study, stem cell researchers Hooman Allayee and Gregor Adams and colleagues performed a genetic screen of a collection of more than 100 strains of mouse DNA known as the hybrid mouse diversity panel, frequently used by scientists in the laboratory.

They found that different strains had different amounts of several important sub-populations of blood stem cells, including those known as short-term HSCs, which are what cause red and white blood cells to form in adults. They also linked the activation of a gene called Hopx to an increase in the amount of short-term HSC, and found that rodents lacking this specific gene formed fewer short-term HSCs and were largely ineffective bone marrow donors.

Technique could help find genes behind other stem cell systems

Allayee, Adams, and their co-authors explained that they conducted a genome-wide association study (GWAS) using the hybrid mouse diversity panel in order to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC) frequency. They said they found “several loci” that were “significantly associated with HSPC frequency,” including Hopx.

This gene had previously been implicated in the development of cardiac issues, but had not been linked to HSPC biology until now. They detected reduced cell frequencies and impaired engraftment in the competitive repopulation assays of mice lacking the gene, and by doing so, they proved that this method could be used to identify genetic determinants of other stem cell systems.

“Short-term HSCs are the major stem cells in the adult bone marrow, so finding “This powerful genetics platform has the potential to reveal the genes underlying other stem cell populations or a wide range of diseases that would be difficult to study in humans,” Allayee added.


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