Significant Quantitative and Qualitative Transition in Pituitary Stem /  Progenitor Cells Occurs during the Postnatal Development of the Rat Anterior Pituitary

Abstract

We reported recently that a pituitary-specific transcription factor PROP1 is present in SOX2-positive cells and disappears at the early stage of the transition from progenitor cell to committed cell during the embryonic development of the rat pituitary. In the present study, we examined the localisation and identification of SOX2-positive and PROP1/SOX2-positive cells in the neonatal and postnatal rat pituitaries by immunohistochemistry. Quantitative analysis of immunoreactive cells demonstrated that SOX2-positive pituitary stem/progenitor cells are not only predominantly localised in the marginal cell layer, but also are scattered in the parenchyma of the adult anterior lobe. In the marginal cell layer, the number of PROP1/SOX2-positive cells significantly decreased after postnatal day 15, indicating that a significant quantitative transition is triggered in the marginal cell layer during the first postnatal growth wave of the anterior pituitary. By contrast, other phenotypes of SOX2-positive stem/progenitor cells that express S100β appeared in the postnatal anterior pituitary. These data suggested that quantitative and qualitative transition occurs by acquisition of a novel mechanism in terminal differentiation in the postnatal development of the anterior pituitary.

Pituitary stem cell regulation: who is pulling the strings?

“…Further refinement pinpointed a SP subfraction (referred to as the stem cellside population or SC-SP) highly enriched in cells with stem cell characteristics and expressing stemness markers, in particular SOX2 and SOX9 ). These and other markers (including E-cadherin, glial cell line derived neurotrophic factor family receptor alpha 2 or GFRA2, nestin and PROP1) were found in the cells of the marginal zone bordering the cleft (Fauquier et al 2008, Gleiberman et al 2008, GarciaLavandeira et al 2009, Yoshida et al 2011, with a similar expression and organization picture in human pituitary (Garcia-Lavandeira et al 2009. In addition, SOX2 + cells were also found within the gland's parenchyma, mostly occurring in clusters and also expressing SOX9 and E-cadherin (Fauquier et al 2008, Chen et al 2013, Nantie et al 2014, Zhu et al 2015.…”

“…However, whether the stem cells at the different locations exhibit different properties, regulation and function is not clear. Some reports point to molecular distinctions, including differential expression of PROP1 and extracellular matrix components (Yoshida et al 2011(Yoshida et al , 2016a.…”

“…During the neonatal growth wave, pituitary stem cells are more abundant and more proliferative as compared to the stem cells in the adult gland and show higher expression of several components of key embryonic pathways like sonic hedgehog (SHH) and wingless-type MMTV integration site (WNT) (Yoshida et al 2011. In accordance, lineage tracing studies showed a larger contribution of the pituitary SOX2 + and SOX9 + stem cells to endocrine cells at young age than at adult age when pituitary turnover is very low, indicating that the stem cells are (more) active in early-postnatal maturation but largely quiescent under adult homeostatic conditions (Andoniadou et al 2013.…”

Pituitary Stem Cells During Normal Physiology and Disease

“…In time, additional markers of cells with this in vitro self-renewal capacity have been put forward to refine the characterisation of PSCs, including Nestin, PROP1, SOX9, GFRα2 and PRX1/2 (Gleiberman et al 2008;Yoshida et al 2009;Rizzoti et al 2013;GarciaLavandeira et al 2009;Higuchi et al 2014). In the postnatal rodent gland in vivo, SOX2-positive cells displayed a high degree of overlap with other proposed stem cell markers such as SOX9 (Rizzoti et al 2013), PROP1 (Yoshida et al 2009(Yoshida et al , 2011, and PRX1/2 (Higuchi et al 2014). We confirmed that SOX2-positive cells did not overlap with differentiation markers but we sought to determine if they were able to give rise to all the differentiated lineages in vivo.…”

Pituitary Stem Cells: Quest for Hidden Functions

“…This transcription factor, which -among others -is essential for the regulation and migration of RP progenitor cells during pituitary embryogenesis (Himes and Raetzman 2009;Ward et al 2005;Zhu et al 2005Zhu et al , 2007, is expressed in the SOX2 þ cells, although it is not clear yet whether postnatal expression in the MZ stops after the first postnatal weeks or is continuous throughout life (Garcia-Lavandeira et al 2009;Yoshida et al 2009Yoshida et al , 2011. In general, there is no co-localization of PROP1 or SOX2 with hormones (Chen et al 2009;Fauquier et al 2008;Fu et al 2012a,b;Garcia-Lavandeira et al 2009;Gremeaux et al 2012;Yoshida et al 2009), supporting the general notion that stem cell conservators must be downregulated before differentiation starts.…”