Biology subjects

Sheridan, D.

Publications and source records attributed to Sheridan, D..

3 recordsLinked to original sources

bioRxiv2024

Gonadotrophs have a dual origin, with most derived from pituitary stem cells during minipuberty.

Gonadotrophs are the essential pituitary endocrine cells for reproduction. They produce both luteinizing (LH) and follicle-stimulating (FSH) hormones that act on the gonads. Gonadotrophs first appear in the embryonic pituitary, along with other endocrine cell types, and all expand after birth. We show here that most gonadotrophs originate from a population of postnatal pituitary stem cells during minipuberty, while those generated in the embryo are maintained, revealing an unsuspected dual origin of the adult population. This has implications for our understanding of the establishment and regulation of reproductive functions, both in health and in disease.

developmental biology↗

bioRxiv2022

Pituitary stem cells differ according to their position in the gland and maintenance of their progeny depends on physiological context

Stem cell (SC) differentiation and maintenance of resultant progeny underlie cell-turnover in many organs, but it is difficult to pinpoint the contribution of either process. In the pituitary, a central regulator of endocrine axes, adult SCs undergo activation following target organ ablation, providing a well-characterized paradigm to study an adaptative response in a multi-organ system. Here we used single cell technologies to characterize SC heterogeneity and mobilization together with lineage tracing. We show that SC differentiation occurs more frequently than thought previously. In adaptative conditions, differentiation increases and is more diverse than demonstrated by the lineage tracing experiments. Detailed examination of SC progeny suggests that maintenance of selected nascent cells underlies SC output, highlighting a trophic role for the microenvironment. Analyses of cell trajectories further predict pathways and potential new regulators. Our model provides a valuable system to study the influence of evolving states on the mechanisms of SC mobilization. Teaser: Pituitary stem cells are diverse and differentiate more than thought but only selected progeny persist according to need.

developmental biology↗

bioRxiv2020

The calcium binding protein S100β marks Hedgehog-responsive perivascular stem cells that contribute to intimal thickening following iatrogenic flow restriction

A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening. While medial SMCs contribute, the participation of hedgehog responsive resident vascular stem cells (vSCs) to lesion formation remains unclear. Using transgenic eGFP mice and genetic lineage tracing of S100{beta} vSCs in vivo, we identified S100{beta}/Sca1 cells derived from a S100{beta} non-SMC parent population within lesions that co-localise with smooth muscle -actin (SMA) cells following iatrogenic flow restriction, an effect attenuated following hedgehog inhibition with the smoothened inhibitor, cyclopamine. In vitro, S100{beta}/Sca1 cells isolated from atheroprone regions of the mouse aorta expressed hedgehog signalling components, acquired the di-methylation of histone 3 lysine 4 (H3K4me2) stable SMC epigenetic mark at the Myh11 locus and underwent myogenic differentiation in response to recombinant sonic hedgehog (SHh). Both S100{beta} and PTCH1 cells were present in human vessels while S100{beta} cells were enriched in arteriosclerotic lesions. Recombinant SHh promoted myogenic differentiation of human induced pluripotent stem cell-derived S100{beta} neuroectoderm progenitors In vitro. We conclude that hedgehog responsive S100{beta} vSCs contribute to lesion formation and support targeting hedgehog signalling to treat subclinical arteriosclerosis.

cell biology↗