The pituitary represents the endocrine master regulator. In mouse, the gland undergoes active maturation immediately after birth. Here, we in detail portrayed the stem cell compartment of neonatal pituitary. Single-cell RNA-sequencing pictured an active gland, revealing proliferative stem as well as hormonal (progenitor) cell populations. The stem cell pool displayed a hybrid epithelial/mesenchymal phenotype, characteristic of development-involved tissue stem cells. Organoid culturing recapitulated the stem cells’ phenotype, interestingly also reproducing their paracrine activity. The pituitary stem cell-activating interleukin-6 (IL-6) advanced organoid growth, although the neonatal stem cell compartment was not visibly affected in Il6-/- mice, likely due to cytokine family redundancy. 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. 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. Together, our study decodes the stem cell compartment of neonatal pituitary, exposing an activated state in the maturing gland. Understanding stem cell activation is key to potential pituitary regenerative prospects.
scRNA-seq data have been deposited in ArrayExpress (E-MTAB-11337). All other study data are included in the article and/or supportinginformation.
Single-cell Transcriptomics Reveals the Divergent Developmental Lineage Trajectories during Human Pituitary DevelopmentNCBI Gene Expression Omnibus, GSE142653.
- Emma Laporte
- Annelies Vennekens
- Charlotte Nys
- Benoit Cox
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Mice with C57BL/6 background were used for the experiments, which were approved by the KU Leuven Ethical Committee for Animal Experimentation (P153/2018).
- T Rajendra Kumar, University of Colorado, United States
- Received: November 22, 2021
- Accepted: June 13, 2022
- Accepted Manuscript published: June 14, 2022 (version 1)
© 2022, Laporte et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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