First specific mechanism of stem-cell niche generation revealed
The mechanism behind the regulation of stem-cell niche generation in bone marrow has been revealed, potentially leading to improvements in stem cell transplantation.
In a recent study, a team of researchers from Columbia University Irving Medical Centre (CUIMC; NY, USA) has uncovered the mechanism that creates stem-cell niches in bone marrow by analyzing gene activity during and after niche creation in mice, aiming to identify the regulation of niche formation. By exploring niche generation, the researchers aim to improve the success rate of stem cell transplantation – an important milestone in patient transplant recovery.
For approximately one in every ten patients, stem cell transplantation fails due to poor engraftment of transplanted cells, which can often be fatal if infection or bleeding events occur.
When exploring the gene activity of mouse bone marrow cells during and after niche creation, the team noticed that the Mettl3 gene, involved in mRNA processing and RNA methylation – specifically the m6A modification of mRNA – was highly expressed during creation, but not after.
Are bone marrow-derived mesenchymal stem cells the key to treating Crohn’s disease?
Researchers have demonstrated that human mesenchymal stem cells (hMSCs) can promote healing and tissue regeneration in a mouse model of Crohn’s disease.
The researchers also found that in the absence of Mettl3 during formation, there was an adverse effect on niche generation on the quantity and quality of the stem cell niches in the bone marrow, an increase in bone cells and a decrease in hematopoietic stem cells in the bone marrow. However, after formation, the absence of Mettl3 did not affect the maintenance of the stem-cell niche. Additionally, they identified that Klf2, a target of the Mettl3 protein, requires m6A modifications to be suppressed and therefore enable niche development.
This discovery highlights the potential to modulate gene function to create more niches, generate niche organoids in the laboratory and possibly improve the efficacy of stem-cell transplants to the bone marrow.
Excited to have uncovered the first genetically regulated mechanism of niche creation, the team is now focusing on translating their findings into patient applications. First, they aim to enhance niche creation, starting with adult mice, as they are currently unable to expand the niche cells to the numbers required for translational approaches.
Commenting on the potential of the study, senior author Lei Ding (CUIMC) stated that, “if we can create a niche in the lab, we can better understand how the niche supports stem cells and maybe use such systems to generate more stem cells for patient transplants.”
