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RUNX1 标记了在前列腺发育起始时建立的腔细胞雄激素抵抗谱系。

RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development.

机构信息

Cancer Research United Kingdom, Stem Cell Biology Group, Cancer Research United Kingdom Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, United Kingdom.

Cancer Research United Kingdom, Prostate Oncobiology Group, Cancer Research United Kingdom Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, United Kingdom.

出版信息

Elife. 2020 Oct 7;9:e60225. doi: 10.7554/eLife.60225.

DOI:10.7554/eLife.60225
PMID:33025905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7644213/
Abstract

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.

摘要

前列腺上皮细胞层次结构和谱系异质性的特征对于理解其再生特性和恶性肿瘤至关重要。在这里，我们报告转录因子 RUNX1 标记了一个特定的近端腔细胞（PLC）亚群，该亚群在发育中和成年小鼠前列腺的尿道周围区域富集，与先前鉴定的 NKX3.1 腔抗去势细胞不同。通过 scRNA-seq 分析和遗传谱系追踪，我们表明 RUNX1 PLC 不受雄激素剥夺的影响，并且不会促进远端腔室的再生。此外，我们证明在胚胎前列腺特化开始时出现了一个转录上相似的 RUNX1 群体，以填充导管的近端区域。总的来说，我们的结果表明 RUNX1 PLC 是一种内在的抗去势和自我维持的谱系，它在前列腺发育早期出现，并为前列腺上皮的谱系关系提供了新的见解。

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