![]() 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. injured the newborn pituitary gland, the gland was able to fully regenerate, despite the stem cells not becoming more activated. It had already been established that the adult pituitary stem cells become activated upon injury, and that the gland has some regenerative capacity. also wanted to know whether the newborn pituitary gland responded to injury differently than the adult gland. Both findings support the notion that WNT signalling is required to establish the activated state of the maturing pituitary gland in newborn mice. Furthermore, blocking the pathway directly in newborn mice reduced the number of dividing stem cells in the pituitary gland. blocked WNT signalling in these organoids, the organoids failed to form or divide. used an organoid system that allowed them to recapitulate the stem cell compartment of the maturing pituitary gland in a dish. To confirm these findings, 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. ![]() 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. The researchers compared the cells of the maturing pituitary gland of newborn mice to the cells in the established gland of adult mice. 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. However, it remains unclear how the activated state found in the maturing gland is established and regulated. 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. These stem cells can divide to produce more cells like themselves, or differentiate into cells of different types, including hormone-producing cells. To perform its role, the pituitary gland needs specialised hormone-producing cells, but it also contains stem cells. 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. Understanding stem cell activation is key to potential pituitary regenerative prospects. Together, our study decodes the stem cell compartment of neonatal pituitary, exposing an activated state in the maturing gland. Following local damage, the neonatal gland efficiently regenerates, despite absence of additional stem cell proliferation, or upregulated IL-6 or WNT expression, all in line with the already high stem cell activation status, thereby exposing striking differences with adult pituitary. Further transcriptomic analysis exposed a pronounced WNT pathway in the neonatal gland, shown to be involved in stem cell activation and to overlap with the (fetal) human pituitary transcriptome. The pituitary stem cell-activating interleukin-6 advanced organoid growth, although the neonatal stem cell compartment was not visibly affected in Il6 −/− mice, likely due to cytokine family redundancy. Organoid culturing recapitulated the stem cells’ phenotype, interestingly also reproducing their paracrine activity. The stem cell pool displayed a hybrid epithelial/mesenchymal phenotype, characteristic of development-involved tissue stem cells. Single-cell RNA-sequencing pictured an active gland, revealing proliferative stem as well as hormonal (progenitor) cell populations. Here, we in detail portrayed the stem cell compartment of neonatal pituitary. In mouse, the gland undergoes active maturation immediately after birth. The pituitary represents the endocrine master regulator.
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