Together with the Stojilkovic lab and the Genomics core of NICHD, we have initiated a new direction in these studies, single-cell RNAseq analysis of gene expression in the anterior pituitary. This gland is composed of five hormone producing cell types, glia-like folliculostellate cells, and endothelial and blood cells comprising the pituitary sinusoidal capillary network. Some key lines of inquiry in pituitary physiology include tridimensional organization and intercellular communication among cells, development and regeneration of pituitary cells, and the heterogeneity and function of folliculostellate cells. Great efforts have been dedicated towards these aims, but many of the molecular underpinnings remain unknown. We have carried out the first single-cell transcriptome study of anterior pituitary cells. We profiled over 6700 freshly dispersed cells from postpubertal male and female rats. In addition to confirming known markers, our transcriptome analysis highlights many novel genetic markers contributing to pituitary cell type identity and sexual dimorphism. We provide for the first time an estimate of the percentage of folliculostellate cells, and we identify at least two main subtypes of this heterogeneous cell population. Our data support the hypothesis that folliculostellate cells provide structural support for the hormone producing cells, as they express many genes encoding detoxification enzymes. Our analysis of expression of developmental, stem cell/progenitor, and neuroendocrine markers suggests that folliculostellate and hormone producing cells are sister cells with a common origin. We also provide a detailed view of cell type-dependent expression of genes encoding extracellular matrix, cell adhesion, and endogenous ligand proteins, critical for the tridimensional organization of the anterior pituitary and the cross-talk between its constituent cells. We expect the marker genes identified for pituitary cell types will serve as a solid base for future investigations into pituitary structure, function, and pathophysiology, as well as for the study of postnatal pituitary development, regeneration, and reorganization. A paper has been submitted.
| Fletcher, Patrick A; Sherman, Arthur; Stojilkovic, Stanko S (2018) Common and diverse elements of ion channels and receptors underlying electrical activity in endocrine pituitary cells. Mol Cell Endocrinol 463:23-36 |
| Mackay, Laurent; Zemkova, Hana; Stojilkovic, Stanko S et al. (2017) Deciphering the regulation of P2X4 receptor channel gating by ivermectin using Markov models. PLoS Comput Biol 13:e1005643 |
| Sherman, Arthur S; Ha, Joon (2017) How Adaptation Makes Low Firing Rates Robust. J Math Neurosci 7:4 |
| Fletcher, Patrick A; Zemkova, Hana; Stojilkovic, Stanko S et al. (2017) Modeling the diversity of spontaneous and agonist-induced electrical activity in anterior pituitary corticotrophs. J Neurophysiol 117:2298-2311 |
| Zemkova, Hana; Khadra, Anmar; Rokic, Milos B et al. (2015) Allosteric regulation of the P2X4 receptor channel pore dilation. Pflugers Arch 467:713-26 |
| Khadra, Anmar; Tomic, Melanija; Yan, Zonghe et al. (2013) Dual gating mechanism and function of P2X7 receptor channels. Biophys J 104:2612-21 |
| Khadra, Anmar; Yan, Zonghe; Coddou, Claudio et al. (2012) Gating properties of the P2X2a and P2X2b receptor channels: experiments and mathematical modeling. J Gen Physiol 139:333-48 |
| Matveev, Victor; Bertram, Richard; Sherman, Arthur (2011) Calcium cooperativity of exocytosis as a measure of Caýý+ channel domain overlap. Brain Res 1398:126-38 |
| Yan, Zonghe; Khadra, Anmar; Sherman, Arthur et al. (2011) Calcium-dependent block of P2X7 receptor channel function is allosteric. J Gen Physiol 138:437-52 |
| Tsaneva-Atanasova, Krasimira; Osinga, Hinke M; Riess, Thorsten et al. (2010) Full system bifurcation analysis of endocrine bursting models. J Theor Biol 264:1133-46 |
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