ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study investigated the functional diversity of SOX9-positive pituitary stem cells (PSCs) using sophisticated murine transgenics combined with single-cell mRNA-seq (sc-mRNAsq). It identifies that the ability of Sox9+ve PSCs to maintain progeny varies depending on their location and surrounding context.

The authors elegantly show that the SOX9 transcription factor marks a population of stem cells in the pituitary gland. The authors FAC-sort Sox9+ve cell fraction and submit these to sc-mRNA-sq. This identifies an unexpected finding that Sox9+ve stem cells exhibit distinct characteristics based on their spatial positioning within the pituitary gland, with varying potential for differentiation and progeny maintenance. Under normal physiological conditions, these Sox9+ve stem cells are quiescent and contribute little to new cells. However, the Sox9+ve PSCs are mobilised and activated upon endocrine challenges by the target organ. Hence, adrenalectomy and gonadectomy trigger the activation of this population of cells. Using cell lineage tracing using a Sox9CreERT2, RosaYFP, the authors identify that the regeneration capacity and lineage commitment are dependent on the position. Importantly they show that, independent of the endocrine challenge, all endocrine pituitary cell types are initially generated, but only the required cell type survives. Hence, the local environment influences the fate of these Sox9+ve PSCs, suggesting that stem cell behaviour is not uniform across the pituitary but rather context-dependent.

These findings highlight the importance of microenvironmental factors in regulating stem cell function. The most compelling aspect of this research is its emphasis on the context-specific nature of stem cell maintenance and progeny. By demonstrating that the surrounding microenvironment dictates how these cells behave, the study underscores the importance of studying stem cells in their native niches, rather than in isolation. The identification of which tissue environmental factors are important in mobilising PSCs could be crucial in devising regenerative therapies for pituitary disorders or endocrine diseases.