Department of Cell Biology, New York University School of Medicine, New York, USA.
Department of Dermatology, New York University School of Medicine, New York, USA.
Nat Commun. 2022 Mar 17;13(1):1421. doi: 10.1038/s41467-022-28937-x.
Gpr125 is an orphan G-protein coupled receptor, with homology to cell adhesion and axonal guidance factors, that is implicated in planar polarity and control of cell movements. By lineage tracing we demonstrate that Gpr125 is a highly specific marker of bipotent mammary stem cells in the embryo and of multiple long-lived unipotent basal mammary progenitors in perinatal and postnatal glands. Nipple-proximal Gpr125+ cells express a transcriptomic profile indicative of chemo-repulsion and cell movement, whereas Gpr125+ cells concentrated at invasive ductal tips display a hybrid epithelial-mesenchymal phenotype and are equipped to bind chemokine and growth factors and secrete a promigratory matrix. Gpr125 progenitors acquire bipotency in the context of transplantation and cancer and are greatly expanded and massed at the pushing margins of short latency MMTV-Wnt1 tumors. High Gpr125 expression identifies patients with particularly poor outcome within the basal breast cancer subtype highlighting its potential utility as a factor to stratify risk.
Gpr125 是一种孤儿 G 蛋白偶联受体，与细胞黏附和轴突导向因子具有同源性，参与平面极性和细胞运动的控制。通过谱系追踪，我们证明 Gpr125 是胚胎中多能乳腺干细胞和围产期和产后乳腺中多种长寿单能基底乳腺祖细胞的高度特异性标志物。乳头近端的 Gpr125+细胞表达提示化学排斥和细胞运动的转录组特征，而集中在侵袭性导管尖端的 Gpr125+细胞则表现出混合上皮-间充质表型，并能够结合趋化因子和生长因子并分泌促进迁移的基质。Gpr125 祖细胞在移植和癌症的背景下获得多能性，并在短潜伏期 MMTV-Wnt1 肿瘤的快速推进边缘大量扩增和聚集。高 Gpr125 表达可识别基底乳腺癌亚型中预后特别差的患者，突出了其作为分层风险因素的潜在用途。
