小柯机器人

比利时VIB研究所Kiavash Movahedi小组利用单细胞分析揭示胶质母细胞瘤中巨噬细胞的竞争和分化。该项研究成果于2021年3月29日在线发表在《自然—神经科学》上。

研究人员采用单细胞RNA测序和CITE-seq来绘制了胶质母细胞瘤在小鼠肿瘤以及新诊断的或复发患者中的免疫情况。这揭示了一个大而多样的骨髓区室，其中树突状细胞和巨噬细胞群体在物种间是保守的，并且在疾病阶段间是动态的。肿瘤相关的巨噬细胞（TAM）由小胶质细胞或单核细胞衍生的群体组成，两者均表现出额外的异质性，包括具有保守的脂质和低氧特征的亚群。

小胶质细胞和单核细胞衍生的TAM是自我更新的群体，它们之间竞争空间，并可能通过CSF1R阻断而耗尽。小胶质细胞来源的TAM在新诊断的肿瘤中占主导地位，但在复发后，尤其是在低氧肿瘤环境中，单核细胞来源的TAM数量变多。这项研究结果揭示了胶质母细胞瘤的髓系图谱，并为将来的治疗干预提供了框架。 

据悉，胶质母细胞瘤是侵袭性的原发性脑癌，并会以治疗耐药性肿瘤的形式复发。髓样细胞控制胶质母细胞瘤的恶性，但其在疾病进展过程中的动力学仍知之甚少。

附：英文原文

Title: Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization

Author: Ana Rita Pombo Antunes, Isabelle Scheyltjens, Francesca Lodi, Julie Messiaen, Asier Antoranz, Johnny Duerinck, Daliya Kancheva, Liesbet Martens, Karen De Vlaminck, Hannah Van Hove, Signe Schmidt Kjlner Hansen, Francesca Maria Bosisio, Koen Van der Borght, Steven De Vleeschouwer, Raf Sciot, Luc Bouwens, Michiel Verfaillie, Niels Vandamme, Roosmarijn E. Vandenbroucke, Olivier De Wever, Yvan Saeys, Martin Guilliams, Conny Gysemans, Bart Neyns, Frederik De Smet, Diether Lambrechts, Jo A. Van Ginderachter, Kiavash Movahedi

Issue&Volume: 2021-03-29

Abstract: Glioblastomas are aggressive primary brain cancers that recur as therapy-resistant tumors. Myeloid cells control glioblastoma malignancy, but their dynamics during disease progression remain poorly understood. Here, we employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence. This revealed a large and diverse myeloid compartment, with dendritic cell and macrophage populations that were conserved across species and dynamic across disease stages. Tumor-associated macrophages (TAMs) consisted of microglia- or monocyte-derived populations, with both exhibiting additional heterogeneity, including subsets with conserved lipid and hypoxic signatures. Microglia- and monocyte-derived TAMs were self-renewing populations that competed for space and could be depleted via CSF1R blockade. Microglia-derived TAMs were predominant in newly diagnosed tumors, but were outnumbered by monocyte-derived TAMs following recurrence, especially in hypoxic tumor environments. Our results unravel the glioblastoma myeloid landscape and provide a framework for future therapeutic interventions. Single-cell RNA-seq and CITE-seq were used to profile the glioblastoma immune landscape in humans and mice, revealing the diversity and dynamics of tumor macrophages as the disease progresses from initial diagnosis to recurrence.

DOI: 10.1038/s41593-020-00789-y

Source: https://www.nature.com/articles/s41593-020-00789-y

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex