美國加州大學(xué)舊金山分校Allan Balmain研究團(tuán)隊(duì)發(fā)現(xiàn)，干細(xì)胞狀態(tài)在皮膚鱗狀細(xì)胞癌的多階段發(fā)展中趨同。2024年5月31日出版的《科學(xué)》雜志發(fā)表了這項(xiàng)成果。
研究人員從數(shù)百個(gè)小鼠組織樣本（包括正常組織和腫瘤組織）中創(chuàng)建了基因表達(dá)網(wǎng)絡(luò)，并將其與系譜追蹤和單細(xì)胞RNA-seq整合在一起，以確定惡性腫瘤前期細(xì)胞中表達(dá)譜系可塑性和耐藥性標(biāo)記的細(xì)胞狀態(tài)的趨同性。
其中兩種代表多譜系可塑性或增殖的細(xì)胞狀態(tài)成反比，表明兩者之間存在相互排斥的關(guān)系。用化療治療體內(nèi)癌細(xì)胞可抑制增殖狀態(tài)并激活多譜系可塑性，而抑制分化則可抑制可塑性并增強(qiáng)對細(xì)胞周期抑制劑的反應(yīng)。對這一細(xì)胞狀態(tài)轉(zhuǎn)換點(diǎn)的操縱可能為癌癥治療提供潛在的組合靶點(diǎn)。
據(jù)悉，干細(xì)胞對細(xì)胞異質(zhì)性、譜系可塑性和耐藥性起著至關(guān)重要的作用。
附：英文原文
Title: Stem-cell states converge in multistage cutaneous squamous cell carcinoma development
Author: Mark A. Taylor, Eve Kandyba, Kyle Halliwill, Reyno Delrosario, Matvei Khoroshkin, Hani Goodarzi, David Quigley, Yun Rose Li, Di Wu, Saumya R. Bollam, Olga K. Mirzoeva, Rosemary J. Akhurst, Allan Balmain
Issue&Volume: 2024-05-31
Abstract: Stem cells play a critical role in cancer development by contributing to cell heterogeneity, lineage plasticity, and drug resistance. We created gene expression networks from hundreds of mouse tissue samples (both normal and tumor) and integrated these with lineage tracing and single-cell RNA-seq, to identify convergence of cell states in premalignant tumor cells expressing markers of lineage plasticity and drug resistance. Two of these cell states representing multilineage plasticity or proliferation were inversely correlated, suggesting a mutually exclusive relationship. Treatment of carcinomas in vivo with chemotherapy repressed the proliferative state and activated multilineage plasticity whereas inhibition of differentiation repressed plasticity and potentiated responses to cell cycle inhibitors. Manipulation of this cell state transition point may provide a source of potential combinatorial targets for cancer therapy.
來源：科學(xué)網(wǎng)
原標(biāo)題：干細(xì)胞狀態(tài)在皮膚鱗狀細(xì)胞癌的多階段發(fā)展中趨同
作者：小柯機(jī)器人