Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:NR5A1 is expressed in the pituitary gonadotropes and regulates their functional differentiation. We have previously identified a pituitary-specific enhancer region located in the 6th intron of the Nr5a1 gene. In this study, deletion of the pituitary enhancer by genome editing abolished the expression of NR5A1 in the pituitary gland, confirming the functional importance of the enhancer. Transcriptomic changes in the enhancer-deleted mouse pituitary were revealed in both males and females.
Project description:Mutations in the pituitary specific transcription factor Prophet of Pit-1 (PROP1) are the most common genetic etiology of combined pituitary hormone deficiency (CPHD). CPHD is associated with short stature, attributable to growth hormone deficiency and/or thyroid stimulating hormone deficiency, as well as hypothyroidism and infertility. Pathogenic lesions impair pituitary development and differentiation of endocrine cells. We performed single-cell RNA sequencing of pituitary cells from a wild-type and a Prop1-mutant P4 female to elucidate population-specific differential gene expression. We observed a Smoc2+ve population that expressed low Sox2, which trajectory analyses suggest are a transitional cell state as stem cells differentiate into endocrine cells. We also detected ectopic expression of Sox21 in these cells in the Prop1df/df mutant. Prop1-mutant mice are known to overexpress Pou3f4, which we now show to be also enriched in this Smoc2+ve population. We sought to elucidate the role of Pou3f4 during pituitary development and to determine the contributions of Pou3f4 upregulation to pituitary disease by utilizing double-mutant mice lacking both Prop1 and Pou3f4. However, our data showed that Pou3f4 is not required for normal pituitary development and function. Double mutants further demonstrated that the upregulation of Pou3f4 was not causative for the overexpression of Sox21. These data indicate loss of Pou3f4 is not a potential cause of CPHD, and further studies may investigate the functional consequence of upregulation of Pou3f4 and Sox21, if any, in the novel Smoc2+ve cell population.
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Aging is a multifactorial process with significant functional alterations of the human body including endocrinal systems which control the whole-body physiology and metabolism. In this vein, aging-induced decline of endocrine function are associated with multiple physiological and metabolic diseases. However, aging-associated molecular shifts in the pituitary gland, the central organ of the endocrine system, have not been dissected systemically. In this study, we conducted single-cell transcriptomic analysis of the anterior pituitary gland by comparing old and young male mice. Single-cell transcriptomics not only increased the resolution for clustering of various cell types in the pituitary gland, but also enabled detailed analysis of differential expression and intercellular communication caused by aging. In summary, our study constructed the first single-cell transcriptomic atlas of pituitary aging and identified associated features of in a single-cell level, providing resources to develop novel potential therapeutic targets for aging-associated endocrine dysfunction.
Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.
Project description:NR5A1 is expressed in the pituitary gonadotropes and regulates their functional differentiation. In this study, transcriptomes of the pituitary gonadotropes which are sorted from Ad4BP-BAC-EGFP mice were revealed in males and females.