Unusually high levels of a transcription factor called paired related homeobox protein 1 (PRRX1) in human oligodendrocyte progenitor cells hinders their ability to respond to the loss of myelin and to transform into mature, myelin-producing oligodendrocytes, a new study shows.
These findings suggest a new potential way of treating multiple sclerosis (MS), one targeting therapies that can prevent or overcome this block in the maturity of these precursor cells by moving them out of a state called pathological quiescence (inactivity).
The study, “Paired Related Homeobox Protein 1 Regulates Quiescence in Human Oligodendrocyte Progenitors,” was published in the journal Cell Reports.
Oligodendrocytes, the myelin-producing cells, develop from more immature, stem cell-like cells called oligodendrocyte progenitor cells. These are the cells that, upon myelin loss, travel to demyelinated lesion sites where they mature and generate myelin-producing cells.
In vivo loss of a single oligodendrocyte progenitor cell, through death or because they transformed (differentiated) into a mature oligodendrocyte, is a tightly regulated process, but its mechanisms remain poorly defined.
These progenitor cells, much like other stem cell-like cells in adult tissues, exist in a state of dormancy called cellular quiescence. This dormancy is essential for maintaining cell populations in reserve for when a tissue needs regeneration and repair.
In muscle stem cells, loss of quiescence leads to the exhaustion of the stem cell pool and failed regeneration. However, failure to “wake” the cells from this dormant state after an injury — what researchers call pathological quiescence — may also contribute to failed regeneration.
Researchers at the University at Buffalo (UB) had previously identified several transcription factors whose levels were higher in human oligodendrocyte progenitor cells than was seen in progenitor cells that give rise to neurons.
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