Fundamental mechanisms causing pituitary stem cell aging in mice and humans
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE299835 | GEO | 2025/06/27
REPOSITORIES: GEO
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Project description:Fundamental mechanisms causing pituitary stem cell aging in mice and humans
| PRJNA1276598 | ENA
Project description:We recently showed that the mouse pituitary holds regenerative competence. Young-adult GHCre/iDTR mice, expressing diphtheria toxin (DT)-receptor in growth hormone (GH)-producing cells, regenerate the cells ablated by 3-day DT treatment (3DT) up to 60% after 5 months. The pituitary's stem cells were found to participate in this restoration process. Here, we characterized this regenerative capacity in relation to age and recovery period, and started to search for underlying molecular mechanisms. Extending the recovery period (to 19 months) does not result in higher regeneration levels. In addition, the regenerative competence disappears at ageing, coinciding with a reduction in pituitary stem cell number and fitness. Surprisingly, prolonging the DT treatment period in young-adult mice to 10 days (10DT) completely blocks the regeneration. The stem cell compartment still reacts by promptly expanding, and retains in vitro stem cell functionality. To obtain a first view on molecular grounds underlying reparative capacity and/or failure, the stem cell-clustering side population (SC-SP) was analyzed by whole-genome expression analysis. A number of stemness factors and components of the Notch, Shh, Wnt, epithelial-mesenchymal transition (EMT) and Hippo pathways are higher expressed in the SC-SP of the regenerating pituitary (after 3DT) when compared to the basal gland and to the non-regenerating pituitary (after 10DT). Taken together, the regenerative capacity of the pituitary is limited both in age-related terms and final efficacy, and appears to rely on stem cell-associated pathway activation. Dissection of the molecular profiles may eventually identify targets to induce or boost regeneration in situations of (injury-related) pituitary deficiency.
2018-09-03 | GSE72992 | GEO
Project description:Adult pituitary stem cells (SC) are mainly dormant, yet in the case of damage the resident SC compartment shows swift activation. More in particular, following diphtheria toxin (DT)-triggered endocrine cell-ablation injury in the GHCre/iDTR mouse model (expressing the Cre recombinase under control of the Gh promoter, as well as the Cre-inducible DT receptor (iDTR)), the pituitary stem cell population is promptly activated displaying enhanced proliferative activity and expansion. Substantial regeneration of the depleted somatotropes is eventually observed after 5 to 6 months. However, this regenerative competence rapidly drops with age, and is no longer observed when mice get older (from 8-10 months of age). Virtually nothing is known about the molecular machinery driving the quiescent pituitary stem cells into activation (as observed following local injury), neither about how this route may change at advancing age. Here, we started to tackle this query by interrogating young (9-11 weeks) and old (14 months), damaged and undamaged pituitary (specifically, its major endocrine AP lobe) using single-cell RNA sequencing. We focused on the prompt stem cell reaction that occurs immediately upon the DT-induced local damage in the GHCre/iDTR model.
2021-06-15 | E-MTAB-10021 | biostudies-arrayexpress
Project description:The mouse pituitary gland houses a stem cell compartment which is known to suffer from an inflammatory phenotype at middle age (12-15 months), a process commonly referred to as ‘inflammaging’. Here, we investigate the aging pituitary stem cell phenotype by using single-cell RNA-sequencing interrogations of old (24-26 months) normal pituitary. Moreover, we enriched our endeavor by including pituitary damaged state in the single-cell interrogation of old mice. In particular, local damage was inflicted by diphtheria toxin (DT)-triggered endocrine cell-ablation injury using the GHCre/iDTR mouse model (expressing Cre recombinase under control of the growth hormone (Gh) promoter, as well as Cre-inducible (floxed) DT receptor (iDTR)).
2025-01-06 | E-MTAB-14067 | biostudies-arrayexpress
Project description:Rat pituitary organ cultures were treated with either GnRH at 10nM for 6 hours, or treated with control for 6 h, both groups in triplicate; samples were processed to generate total RNA, which were subsequently analyzed for gene expression using Affymetrix rat 230 2.0 arrays Experiment Overall Design: Comparison of gene expression profiles between GnRH-treated and control rat pituitary organ cultures
2008-06-13 | E-GEOD-4865 | biostudies-arrayexpress
Project description:Rat pituitary organ cultures were treated with either GnRH at 10nM for 6 hours, or treated with control for 6 h, both groups in triplicate; samples were processed to generate total RNA, which were subsequently analyzed for gene expression using Affymetrix rat 230 2.0 arrays Keywords: rat pituitary organ culture treated vs control
2006-08-31 | GSE4865 | GEO
Project description:The pituitary gland regulates growth, metabolism, reproduction, the stress response, uterine contractions, lactation, and water retention. It secretes polypeptide hormones in response to hypothalamic input, end organ feedback, and diurnal cues. The mechanisms by which pituitary stem cells are recruited to proliferate, maintain quiescence or differentiate into specific cell types, especially thyrotropes, are not well understood. We utilized single-cell RNA sequencing in juvenile P7 mouse pituitary cells to identify transcription factors in pituitary stem and endocrine populations, with a focus on thyrotrope subpopulations. We first identified common gene regulatory networks activated in proliferating stem and proliferating endocrine cells. We ascertained Shox2 and Sox14 as candidate regulators of pars distalis and pars tuberalis thyrotropes, respectively, and subsequently found reduced hormone expression in Sox14-knockout pars tuberalis thyrotropes. We further discovered dual-identity cells expressing both POU1F1 and NR5A1 and demonstrated that approximately one-third of pars distalis thyrotropes are descended from NR5A1-expressing cells, typically considered gonadotrope progenitors. We have therefore used single-cell transcriptomics to identify novel developmental mechanisms regulating the specification and hormone expression in thyrotrope subpopulations.
2022-09-02 | GSE205418 | GEO
Project description:Several processes governing growth and metabolism are regulated by the neuroendocrine system, particularly the trophic hormones produced in the anterior pituitary gland. However, many of the differences that exist in pituitary gene expression and functional gene networks associated with divergent growth characteristics are still largely unknown. Using the Del-Mar 14K Chicken Integrated Systems microarray, this experiment evaluated global gene expression in the anterior pituitary gland during the first 7 weeks of post-hatch growth in two lines of chickens genetically selected for high growth (HG) or low growth (LG) at SRA-INRA, France. The HG and LG chickens differ in body weight, abdominal fat content, and plasma hormone and metabolite levels, making them a valuable model for both biomedical and agricultural traits. Amplified total RNA extracted from individual anterior pituitary glands collected from 4 birds from each line at each age (n=4) was produced. Cy-3 labeled cDNA from these samples was hybridized with an aliquot of Cy-5 labeled cDNA made from a pool of total RNA from all 32 samples. Data were analyzed as log2-(Cy3intensity (norm)/Cy5intensity (raw)) by two-way ANOVA using a linear mixed model procedure (PROC MIXED; SAS institute Inc., Cary, NC), and a total of 2,310 spots were significantly different (P<0.05) by line (1,100), age (1,058), or the line-by-age interaction (353). Of these, we identified 291 spots representing 263 genes as differentially expressed between HG and LG birds, where there was a >160% difference between the highest expression in one line and the lowest expression in the other and a significant line-by-age (110) or line (181) effect. Four anterior pituitary hormones were contained in this set of differentially expressed genes: thyroid-stimulating hormone ?-subunit, luteinizing hormone ?-subunit, and follicle-stimulating hormone ?-subunit mRNA levels were higher in the HG line; and growth hormone mRNA was elevated in the LG line. Pathway analysis revealed differences in expression between HG and LG lines associated with molecular transport, endocrine system development and function, organ and tissue morphology, and cellular compromise. Potential alteration in pituitary function between the two lines was highlighted in a network containing genes associated with hormone expression and secretion, as well as those potentially involved in pituitary gland morphology and vascularization.
2018-11-15 | GSE122519 | GEO
Project description:The mammalian pituitary gland is a complex organ consisting of hormone-producing cells, anterior lobe folliculostellate cells (FSCs), posterior lobe pituicytes, vascular pericytes and endothelial cells, and Sox2-expressing stem cells. We present single-cell RNA sequencing and immunohistofluorescence analyses of pituitary cells of adult female rats with a focus on the transcriptomic profiles of nonhormonal cell types. Samples obtained from whole pituitaries and separated anterior and posterior lobe cells contained all expected pituitary resident cell types and lobe-specific vascular cell subpopulations. FSCs and pituicytes expressed S100B, ALDOC, EAAT1, ALDH1A1, and VIM genes and proteins, as well as other astroglial marker genes, some common and some cell type-specific. We also found that the SOX2 gene and protein were expressed in ~15% of pituitary cells, including FSCs, pituicytes, and a fraction of hormone-producing cells, arguing against its stem cell specificity. FSCs comprised two Sox2-expressing subclusters; FS1 contained more cells but lower genetic diversity, while FS2 contained proliferative cells, shared genes with hormone-producing cells, and expressed genes consistent with stem cell niche formation, regulation of cell proliferation and stem cell pluripotency, including the Hippo and Wnt pathways. FS1 cells were randomly distributed in the anterior and intermediate lobes, while FS2 cells were localized exclusively in the marginal zone between the anterior and intermediate lobes. These data indicate the identity of the FSCs as anterior pituitary-specific astroglia, with FS1 cells representing differentiated cells equipped for classical FSC roles and FS2 cells exhibiting additional stem cell-like features.
2021-12-12 | GSE184319 | GEO
Project description:The pituitary is the master endocrine gland regulating key physiological processes and houses a stem cell compartment. Despite the application of transgenic in vivo approaches, the pituitary stem cells' phenotype, biology, and role remain unclear. To tackle this question, organoids were developed as in vitro model to unravel pituitary stem cell biology. Pituitary organoids represent 3D cell structures that, under defined culture conditions, self-develop from SOX2-positive stem cells and recapitulate multiple hallmarks of pituitary stem cells. Here, we investigate the organoids' transcriptome starting from single-cell RNA-sequencing of organoids derived from pituitaries of neonatal, young-adult, middle-aged and elderly mice.
2025-01-01 | E-MTAB-14008 | biostudies-arrayexpress