Organoids made from pituitary stem cells. Image credit: Emma Laporte (CC BY 4.0)
The pituitary gland is a pea-sized structure found just below the brain that produces hormones controlling everything from growth and stress to reproduction and immunity. To perform its role, the pituitary gland needs specialised hormone-producing cells, but it also contains stem cells. These stem cells can divide to produce more cells like themselves, or differentiate into cells of different types, including hormone-producing cells.
In mice, the stem cells of the pituitary gland appear to be activated in the first few weeks after birth, and later become ‘quiescent’ (or lazy) in the adult pituitary gland. However, it remains unclear how the activated state found in the maturing gland is established and regulated.
To answer this question, Laporte et al. used single-cell RNA sequencing, a technique that allows researchers to profile which genes are active in individual cells, which can provide vital information about the state and activity of a tissue. The researchers compared the cells of the maturing pituitary gland of newborn mice to the cells in the established gland of adult mice. This analysis revealed that the maturing pituitary gland is a dynamic tissue, with populations of cells that are actively dividing (including the stem cells), which the mature pituitary gland lacks. Additionally, Laporte et al. established the molecular basis for the activated state of the stem cells in the maturing pituitary gland, which relies on the activation of a cell signalling pathway called WNT.
To confirm these findings, Laporte et al. used an organoid system that allowed them to recapitulate the stem cell compartment of the maturing pituitary gland in a dish. When Laporte et al. blocked WNT signalling in these organoids, the organoids failed to form or divide. Furthermore, blocking the pathway directly in newborn mice reduced the number of dividing stem cells in the pituitary gland. Both findings support the notion that WNT signalling is required to establish the activated state of the maturing pituitary gland in newborn mice.
Laporte et al. also wanted to know whether the newborn pituitary gland responded to injury differently than the adult gland. It had already been established that the adult pituitary stem cells become activated upon injury, and that the gland has some regenerative capacity. However, when Laporte et al. injured the newborn pituitary gland, the gland was able to fully regenerate, despite the stem cells not becoming more activated. This is likely because these cells are already activated (or ‘primed’), and do not require further activation to divide and repair the gland with the help of other proliferating cells.
With these results, Laporte et al. shed light on the activated state of the stem cells in the pituitary gland of newborn mice. This provides insight into the role of these stem cells, as well as unveiling possible routes towards regenerating pituitary tissue. This could eventually prove useful in medicine, in cases when the pituitary gland is damaged or removed.
