Maintaining the right niche for blood cell development: Researchers identify genes that contribute to hematopoietic stem cell niche by inhibiting fibrosis in bone marrow – News Azi

In a new study published in Nature Communication, researchers led by Osaka University have shed new light on the role of transcription factors Runx1 and Runx2 in bone marrow microenvironments known as HSC niches. HSC niches are essential for the maintenance of HSCs, which give rise to blood cells.

A major component of HSC niches is a cell type known as reticular abundant cells (RAC) of the chemokine ligand CXC. CAR cells express signaling molecules called cytokines that are important for the maintenance of hematopoietic stem and progenitor cells (HSPCs). The team previously found that CAR cells express a transcription factor called Runx2, which is known to play a role in skeletal development. In this study, they recently discovered that CAR cells also express Runx1, which is known to be essential for the development of hematopoietic stem cells. However, it is completely unknown how Runx transcription factors function in maintaining HSC niches, prompting the research team to investigate this role.

“To assess the impact of Runx transcription factors on bone marrow, we used mouse models in which Runx1 and/or Runx2 were specifically deleted in CAR cells,” says lead author Yoshiki Omatsu.

Researchers found that mice lacking Runx1 in mesenchymal cells, including CAR cells, showed normal bone and bone marrow development, while mice lacking Runx2 showed normal CAR cells and bone marrow. , but short and immature bones. However, mice lacking both Runx1 and Runx2 in CAR cells showed a significant reduction in HSPCs and immune cells, as well as an increase in fibrosis (the abnormal buildup of connective tissue) in the bone marrow. , characteristic of a disease known as myelofibrosis. .

“Our results strongly indicate the essential role of Runx1 and/or Runx2 in inhibiting fibrosis and maintaining the HSC niche,” says lead author Takashi Nagasawa.

The research team also found that in a mouse model of primary myelofibrosis, the expression of Runx1 and Runx2 was reduced while the expression of fibrotic genes was increased, further highlighting the role of Runx1 and Runx2 in inhibiting fibrosis in the bone marrow. Although further work is needed on the subject, these results suggest that Runx1 and Runx2 could be potential targets for the diagnosis and treatment of myelofibrosis.

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Materials provided by Osaka University. Note: Content may be edited for style and length.