小柯机器人

异型细胞间通讯调节腺干细胞多能性
2020-08-27 15:13

比利时布鲁塞尔自由大学(ULB)干细胞与癌症实验室Cdric Blanpain研究组的一项最新研究显示,异型细胞间通讯调节腺干细胞多能性。2020年8月26日的《自然》杂志发表了这项成果。

他们显示LC的敲除可以在小鼠体内和类器官中从多个上皮细胞重新激活多能基底干细胞(BSC)的多能性。大量和单细胞RNA测序显示,LC敲除后,BSC在产生LC之前激活了基底细胞和腔细胞的混合分化程序,这使人联想到在胚胎发育过程中调节多能性的遗传程序。通过从单细胞数据中预测配体-受体对,他们发现由LCs分泌的TNF在正常生理条件下会限制基底细胞(BCs)多能性。

相比之下,LC敲除后,BSC及其后代中的Notch、Wnt和EGFR通路被激活。阻断这些途径,或刺激TNF途径,能够抑制再生诱导的BC多能性。他们的研究表明,LC和BC之间的异型交流对于维持腺上皮干细胞的谱系保真度至关重要。

据了解,腺上皮(包括乳腺和前列腺)由BC和LC组成。许多腺上皮细胞由BSC发育而成,这些细胞在成年后被独特的单能干细胞池所取代。然而,成年单能BSC可以在再生条件下和癌基因表达后重新激活多能性。这表明在正常的生理条件下,一种有效的机制限制了BSC的多能性,尽管该机制的性质尚不清楚。

附:英文原文

Title: Heterotypic cell–cell communication regulates glandular stem cell multipotency

Author: Alessia Centonze, Shuheng Lin, Elisavet Tika, Alejandro Sifrim, Marco Fioramonti, Milan Malfait, Yura Song, Aline Wuidart, Jens Van Herck, Anne Dannau, Gaelle Bouvencourt, Christine Dubois, Nina Dedoncker, Amar Sahay, Viviane de Maertelaer, Christian W. Siebel, Alexandra Van Keymeulen, Thierry Voet, Cdric Blanpain

Issue&Volume: 2020-08-26

Abstract: Glandular epithelia, including the mammary and prostate glands, are composed of basal cells (BCs) and luminal cells (LCs)1,2. Many glandular epithelia develop from multipotent basal stem cells (BSCs) that are replaced in adult life by distinct pools of unipotent stem cells1,3,4,5,6,7,8. However, adult unipotent BSCs can reactivate multipotency under regenerative conditions and upon oncogene expression3,9,10,11,12,13. This suggests that an active mechanism restricts BSC multipotency under normal physiological conditions, although the nature of this mechanism is unknown. Here we show that the ablation of LCs reactivates the multipotency of BSCs from multiple epithelia both in vivo in mice and in vitro in organoids. Bulk and single-cell RNA sequencing revealed that, after LC ablation, BSCs activate a hybrid basal and luminal cell differentiation program before giving rise to LCs—reminiscent of the genetic program that regulates multipotency during embryonic development7. By predicting ligand–receptor pairs from single-cell data14, we find that TNF—which is secreted by LCs—restricts BC multipotency under normal physiological conditions. By contrast, the Notch, Wnt and EGFR pathways were activated in BSCs and their progeny after LC ablation; blocking these pathways, or stimulating the TNF pathway, inhibited regeneration-induced BC multipotency. Our study demonstrates that heterotypic communication between LCs and BCs is essential to maintain lineage fidelity in glandular epithelial stem cells.

DOI: 10.1038/s41586-020-2632-y

Source: https://www.nature.com/articles/s41586-020-2632-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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