JAK/STAT signaling maintains an intermediate cell population during prostate basal cell fates determination

The adult prostate gland is maintained by unipotent basal and luminal stem cells, which can become multipotent during inflammation or cancer. However, the exact adult basal stem cell is unclear. Here, we identified two basal cell populations in mouse prostates: a rare intermediate population expressing luminal markers (termed Basal-B) with a greater capacity for organoid formation and a larger basal population (termed Basal-A). Genetic lineage tracing showed that Basal-B cell represented a transient cell state during prostate homeostasis and androgen-mediated regeneration. Activated JAK/STAT signaling was identified in Basal-B cells, and its inhibition significantly reduced Basal-B markers expression. Inflammation increased Basal-B-to-luminal cell differentiation, but JAK/STAT inhibition notably attenuated this effect. Pten gene deletion increased Nkx3.1-expressing Basal-B like cell population and led to neoplasia. In humans, h-Basal-B cells were more prevalent in benign prostate hyperplasia. Our findings highlight the potential function of JAK/STAT signaling in Basal-B cell and prostate cell fates determination.

成年前列腺由单能基底干细胞与管腔干细胞维持，这两类细胞在炎症反应或癌变过程中可获得多能性。然而，目前尚未明确成体前列腺中确切的基底干细胞类型。本研究在小鼠前列腺中鉴定出两类基底细胞群：一类是罕见的表达管腔标志物的中间细胞群（命名为Basal-B），其类器官形成能力更强；另一类是占比更高的基底细胞群（命名为Basal-A）。遗传谱系示踪实验表明，Basal-B细胞是前列腺稳态维持及雄激素介导的再生过程中的一种瞬时细胞状态。研究发现Basal-B细胞中存在激活的JAK/STAT信号通路，抑制该通路可显著降低Basal-B细胞标志物的表达水平。炎症反应可促进Basal-B细胞向管腔细胞分化，而JAK/STAT通路抑制则可显著削弱这一过程。PTEN基因敲除可增加表达NKX3.1的类Basal-B细胞群，并引发赘生性病变。在人体中，h-Basal-B细胞在良性前列腺增生组织中更为常见。本研究结果揭示了JAK/STAT信号通路在Basal-B细胞及前列腺细胞命运决定中的潜在调控功能。