The characterization of prostate epithelial hierarchy and lineage heterogeneity is critical to understand its regenerative properties and malignancies. Here, we report that the transcription factor RUNX1 marks a specific subpopulation of proximal luminal cells (PLCs), enriched in the periurethral region of the developing and adult mouse prostate, and distinct from the previously identified NKX3.1+ luminal castration resistant cells. Using scRNA-seq profiling and genetic lineage tracing, we show that RUNX1+ PLCs are unaffected by androgen deprivation, and do not contribute to the regeneration of the distal luminal compartments. Furthermore, we demonstrate that a transcriptionally similar RUNX1+ population emerges at the onset of embryonic prostate specification to populate the proximal region of the ducts. Collectively, our results reveal that RUNX1+ PLCs is an intrinsic castration-resistant and self-sustained lineage that emerges early during prostate development and provide new insights into the lineage relationships of the prostate epithelium.
Raw sequencing files and processed gene expression matrices have been deposited in the NCBI Gene Expression Omnibus under the accession number GSE151944. The processed datasets for both mouse adult prostate and UGS prostate explant cultures can be accessed via a searchable R Shiny application available at http://shiny.cruk.manchester.ac.uk/pscapp/. All code used to process data and generate figures is available on a public GitHub repository at https://github.com/glacaud/prostate-scRNAseq.
Runx1 marks a luminal castration resistant lineage established at the onset of prostate developmentNCBI Gene Expression Omnibus, GSE151944.
- Esther Baena
- Georges Lacaud
- Karen Blyth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal experiments were approved by the Animal Welfare and Ethics Review Body (AWERB) of the Cancer Research UK Manchester Institute and conducted according to the UK Home Office Project Licence (PPL 70/8580). Genetic lineage-tracing experiments were performed at the Beatson Biological Services Unit (PPL 70/8645 & P5EE22AEE) and approved by the University of Glasgow AWERB. Mice were maintained in purpose-built facility in a 12-hour light/dark cycle with continual access to food and water. All animal procedures were performed on adult males at least 7 weeks of age. Surgical castration was carried out under aseptic conditions.
- Wilbert Zwart, Netherlands Cancer Institute, Netherlands
© 2020, Mevel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Gene expression has been employed for homologizing body regions across bilateria. The molecular comparison of vertebrate and fly brains has led to a number of disputed homology hypotheses. Data from the fly Drosophila melanogaster have recently been complemented by extensive data from the red flour beetle Tribolium castaneum with its more insect-typical development. In this review, we revisit the molecular mapping of the neuroectoderm of insects and vertebrates to reconsider homology hypotheses. We claim that the protocerebrum is non-segmental and homologous to the vertebrate fore- and midbrain. The boundary between antennal and ocular regions correspond to the vertebrate mid-hindbrain boundary while the deutocerebrum represents the anterior-most ganglion with serial homology to the trunk. The insect head placode is shares common embryonic origin with the vertebrate adenohypophyseal placode. Intriguingly, vertebrate eyes develop from a different region compared to the insect compound eyes calling organ homology into question. Finally, we suggest a molecular re-definition of the classic concepts of archi- and prosocerebrum.
The attachment site of the rotator cuff (RC) is a classic fibrocartilaginous enthesis, which is the junction between bone and tendon with typical characteristics of a fibrocartilage transition zone. Enthesis development has historically been studied with lineage tracing of individual genes selected a priori, which does not allow for the determination of single-cell landscapes yielding mature cell types and tissues. Here, in together with open-source GSE182997 datasets (three samples) provided by Fang et al., we applied Single-cell RNA sequencing (scRNA-seq) to delineate the comprehensive postnatal RC enthesis growth and the temporal atlas from as early as postnatal day 1 up to postnatal week 8. And, we furtherly performed single-cell spatial transcriptomic sequencing on postnatal day 1 mouse enthesis, in order to deconvolute bone-tendon junction (BTJ) chondrocytes onto spatial spots. In summary, we deciphered the cellular heterogeneity and the molecular dynamics during fibrocartilage differentiation. Combined with current spatial transcriptomic data, our results provide a transcriptional resource that will support future investigations of enthesis development at the mechanistic level and may shed light on the strategies for enhanced RC healing outcomes.