Researchers at Osaka University have made a new discovery about a molecule which is key for regulating hematopoietic stem cells and progenitor cells.
The regulatory molecule, Ragnase-1, ensures that there is an appropriate supply of blood cells while avoiding the excessive proliferation associated with conditions such as leukaemia. The researchers have assessed in molecule’s role in the renewal and differentiation of hematopoietic stem cells and progenitor cells and how the dysfunction of this molecule can lead to an inability to regulate blood cell production. The inability to regulate blood cell production can have adverse effects such as the development of blood-based malignancies.
Hematopoietic stem cells in mice
Part of their analysis were experiments where one of more copies of the Ragnase-1 gene was deleted in mice, followed by evaluations of stem cell differentiation into other blood cell lineages, and the overall mice health.
The corresponding author Nobuyuki Takakura explained: “Our findings showed that the deletion of both or even just one of the copies of Ragnase-1 led to abnormalities in the renewal and differentiation of HSPCs from the bone marrow. The Ragnase-1 knockout mice also showed physiological abnormalities like weight loss and an enlarged spleen–and they died at a young age.”
The lead author Hiroyasu Kidoya added: “Our findings showed that this activity of Ragnase-1 is key to determining whether stem cells remain in a quiescent state, self-renew to maintain a pool of such cells for future differentiation, or start to differentiate into the various blood cell lineages depending on the current needs of the body.”
The research paper
The finding about Ragnase-1’s role in the self-renewal and differentiation of hematopoietic stem cells and progenitor cells provides a new target for therapeutic strategies for diseases such as leukaemia.
The article is titled “Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis” and is published in Nature Communications.