PubMed HealthSearch

Biomedical subjects

James Kaufman-Cook

Publications and source records attributed to James Kaufman-Cook.

2 recordsLinked to original sources

The role of stem cells in pituitary tumour formation.

Pituitary tumours are intracranial neoplasms that pose significant clinical challenges due to their potential for recurrence, therapeutic resistance and resultant endocrine dysfunction and mass effects. In the normal anterior pituitary, resident pituitary stem cells (PSCs) contribute to tissue homeostasis and cellular turnover. The extent to which PSCs contribute to tumourigenesis is not known, but an increasing number of studies have been aiming to address this. In this review, we summarise current evidence implicating PSCs and tumour stem-like populations in pituitary tumour biology, including potential roles in tumour initiation, maintenance and progression. We outline practical criteria for defining tumour stem cells and evaluate findings from functional studies of human tumours, emerging single-cell and spatial transcriptomic datasets and murine lineage-tracing models. We also provide a curated overview of published single-cell RNA sequencing studies of pituitary tumours, highlighting reported stem/progenitor populations and transcriptional signatures across tumour subtypes and propose a framework for future genomic analyses. Finally, we discuss the translational implications of these findings, including the potential for targeting stem-like populations and their associated signalling pathways.

Humans

Genome-wide association meta-regression identifies stem cell lineage orchestration as a key driver of acne risk.

Over 85% of the population experience acne at some point in their lives, with its severity spanning a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate to severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition. The analytical approach taken in this study aimed to address the impact of variation in the dichotomisation of acne case control status, driven by ascertainment and study design, on effect size estimates across independent genetic association studies of acne. Through a fixed intercept meta-regression framework, we combined evidence genome-wide for association with acne across studies in which case-control status had been ascertained in different settings, allowing for different severity threshold definitions. Across a combined sample of 73,997 cases and 1,103,940 controls of European, South Asian and African American ancestry we identify genetic variation at 165 genomic loci that influence acne risk. There is evidence for both shared and ancestry specific components to the genetic susceptibility to acne and for sex differences in the magnitude of effect of risk alleles at three loci. We observe that common genetic variation explains 13.4% of acne heritability on the liability scale. Consistent with the hypothesis that genetic risk primarily operates at the level of individual pilosebaceous units, a polygenic score derived from this case-control study of acne susceptibility is associated with both self-reported and clinically assessed acne severity in adolescence, further strengthening the link between genetic risk and disease severity. Prioritisation of causal genes at the identified acne risk loci, provides genetic validation of the targets of established and emerging acne therapies, including retinoid treatments. The identified acne risk loci are enriched for genes encoding downstream effectors of RXRA signalling, including SOX9 and components of the WNT and p53 pathways. Illustrating that the control of stem cell lineage plasticity and cellular fate are important mechanisms through which genetic variation influences acne susceptibility within the pilosebaceous unit.

Journal Article