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研究揭示星形细胞转分化促进髓母细胞瘤生长的机制
作者：小柯机器人 发布时间：2020/2/4 8:34:53

近日，美国维吉尼亚大学Hui Zong及其团队的最新工作表明，星形细胞的转分化实现了髓母细胞瘤肿瘤生长所需的多细胞旁分泌反馈回路。这一研究成果2020年1月23日在线发表在国际学术期刊《细胞》上。

通过使用被称为双标记镶嵌分析（MADM）的小鼠遗传系统，研究人员报道了在SHH（sonic hedgehog）激活的髓母细胞瘤（起源于大脑中的单潜能颗粒神经元祖细胞）中，单细胞分辨率下肿瘤微环境（TME）的演化。首先，研究人员发现TME中的星形胶质细胞（TuAstrocytes）是从肿瘤颗粒神经元前体细胞（GNP）转分化而来的，它们正常情况下不会分化为星形胶质细胞。其次，研究人员确定了TME产生的IGF1促进肿瘤进展。第三，研究人员发现胰岛素样生长因子1（IGF1）是由肿瘤相关的小胶质细胞响应白介素4（IL-4）刺激而产生的。最后，研究人员发现IL-4是由TuAstrocytes分泌的。总的来说，这项研究揭示了在髓母细胞瘤的TME内产生多边网络的进化过程：一部分肿瘤细胞转分化为TuAstrocyte，而后者又产生IL-4，刺激小胶质细胞产生IGF1，从而促进肿瘤进展。
 
据介绍，TME对于肿瘤进展至关重要。然而，由于其复杂的细胞组成，TME的建立和功能仍然不清楚。
 
附：英文原文

Title: Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth

Author: Maojin Yao, P. Britten Ventura, Ying Jiang, Fausto J. Rodriguez, Lixin Wang, Justin S.A. Perry, Yibo Yang, Kelsey Wahl, Rowena B. Crittenden, Mariko L. Bennett, Lin Qi, Cong-Cong Gong, Xiao-Nan Li, Ben A. Barres, Timothy P. Bender, Kodi S. Ravichandran, Kevin A. Janes, Charles G. Eberhart, Hui Zong

Issue&Volume: January 23, 2020

Abstract: The tumor microenvironment (TME) is critical for tumor progression. However, the establishmentand function of the TME remain obscure because of its complex cellular composition.Using a mouse genetic system called mosaic analysis with double markers (MADMs), wedelineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activatedmedulloblastomas that originate from unipotent granule neuron progenitors in the brain.First, we found that astrocytes within the TME (TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally neverdifferentiate into astrocytes. Second, we identified that TME-derived IGF1 promotestumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) isproduced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation.Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studiesreveal an evolutionary process that produces a multi-lateral network within the TMEof medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microgliato produce IGF1 to promote tumor progression.

DOI: 10.1016/j.cell.2019.12.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31386-8

期刊信息
Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216
官方网址：https://www.cell.com/