Complex remodeling of the bone marrow microenvironment occurs in primary myelofibrosis (MF), a new study published in Cell Stem Cell found. According to the study, Sox10-positive glial cells expand in primary MF, and ablating them reduces fibrosis. These findings suggest that these cells could be a promising therapeutic target for the disease.
Read more about the pathophysiology of MF
To shed light on stromal alterations occurring in primary MF, a team of researchers led by Lei Ding, PhD, from the Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, Department of Microbiology and Immunology at Columbia University Irving Medical Center in New York, New York performed cell lineage tracing.
The team identified leptin receptor-positive mesenchymal cells as the main precursors of collagen-expressing myofibroblasts. On the contrary, only a few collagen-expressing myofibroblasts derived from Gli1-lineage cells. In fact, deleting Gli1 did not have an impact on primary MF.
Using single-cell RNA sequencing, the researchers confirmed that almost all myofibroblasts originated from LepR-lineage cells. These cells had reduced expression of hematopoietic niche factors and increased expression of fibrogenic factors.
At the same time, arteriolar signature genes were upregulated in endothelial cells and pericytes and Sox10-positive glial cells expanded excessively, suggesting important functional roles in the disease.
When the researchers ablated the glial cells in the bone marrow chemically or genetically, they observed that fibrosis was reduced. Moreover, this improved other pathological features of the disease.
“Thus, [primary MF] involves complex remodeling of the bone marrow microenvironment, and glial cells represent a promising therapeutic target,” they concluded.
MF is a rare hematologic disorder characterized by bone marrow scarring due to the production of excess fibrous tissue, which interferes with the normal production of blood cells. Primary MF occurs idiopathically in the absence of underlying conditions but can be linked to genetic mutations in some cases.
Sarkaria SM, Zhou J, Bao S, et al. Systematic dissection of coordinated stromal remodeling identifies Sox10+ glial cells as a therapeutic target in myelofibrosis. Cell Stem Cell. Published online June 1, 2023. doi:10.1016/j.stem.2023.05.002