Single-Cell RNA-Seq Reveals Heterogeneity of Cell Communications between Schwann Cells and Fibroblasts within Vestibular Schwannoma Microenvironment

Xu, Maoxiang; Wang, Sheng-Ming; Jiang, Yan; Wang, Jingjing; Xiong, Yuanping; Wang, Dong; Yao, Qinke; Xing, Yazhi; Liu, Feng; Chen, Zhengnong; Yu, Dongzhen

doi:10.1016/j.ajpath.2022.06.006

Cited by 12 publications

(13 citation statements)

References 78 publications

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“…We next constructed the linear single‐cell trajectories of gene expression changes using the Monocle package (Trapnell et al, 2014), as previously reported (Xu et al, 2022). Monocle clustering identified 5 cellular clusters, consistent with Seurat clustering (Figure 3f).…”

Section: Resultsmentioning

confidence: 99%

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Single‐cell RNA‐seq uncovers novel metabolic functions of Schwann cells beyond myelination

Eid

Noureldein

Kim

et al. 2023

Journal of Neurochemistry

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Prediabetes and type 2 diabetes have reached epidemic proportions, particularly in countries consuming a Western-type diet. Prediabetes affects 541 million people and 537 million are living with type 2 diabetes (Sun et al., 2022). Both prediabetes and type 2 diabetes can produce damage to the peripheral and autonomic nervous systems.Generally referred to as polyneuropathies, these heterogeneous disorders are caused by diffuse and focal nervous system damage and occur in more than 30% of prediabetic and 50% of type 2 diabetic patients (Callaghan et al., 2015;Elafros et al., 2022;Feldman et al., 2019). The most common type of injury, which we will refer to

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Section: Resultsmentioning

confidence: 99%

“…To identify distinct trajectories among different cell clusters, we used Monocle 3 R package (RRID:SCR_018685) (Trapnell et al, 2014), as previously reported (Xu et al, 2022). The preprocessed scRNA-seq data obtained from Seurat were converted to a cell_data_set object using SeuratWrappers package (RRID:SCR_022555).…”

Section: Trajectory Analysismentioning

confidence: 99%

Single‐cell RNA‐seq uncovers novel metabolic functions of Schwann cells beyond myelination

Eid

Noureldein

Kim

et al. 2023

Journal of Neurochemistry

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“…The concept that Schwannomas arise as a consequence of injurious stimuli to peripheral nerves is evidenced by recent single-cell transcriptomic and epigenetic studies where nerve injury-like states were discovered, and characterised by myeloid cell infiltration 49,50 . Our analyses further support this finding, whereby we illustrate that alternatively-activated TAMs significantly interact with PanCK+ SOX-10+ Schwann cells in both Antoni A and B regions; cell populations expressing both PanCK and vimentin (which is present on all Schwann cell populations we identified) are associated with wound healing responses 51 , which mirror the function of alternatively-activated TAMs.…”

Section: Discussionmentioning

confidence: 99%

High-Dimensional Imaging of Vestibular Schwannoma Reveals Distinctive Immunological Networks Across Histomorphic Niches inNF2-related Schwannomatosis

Jones,

Haley,

Gregory

et al. 2024

Preprint

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NF2-related Schwannomatosis (NF2 SWN) is a rare tumour-predisposition syndrome characterised by the growth of multiple central and peripheral nervous system neoplasms. The drivers of NF2 SWN are pathogenic variants in the tumour suppressor gene NF2, encoding the protein Merlin, leading to development of bilateral vestibular schwannoma (VS) in >95% of patients. VS tumours are characterised by infiltration of myeloid cells and lymphocytes, highlighting the potential of immunotherapy for VS. However, the immunological landscape in VS and the spatial determinants within the tumour microenvironment that shape the trajectory of disease are presently unknown. In this study, to elucidate the complex immunological networks across VS, we performed imaging mass cytometry (IMC) on clinically annotated VS samples from NF2 SWN patients. We reveal the heterogeneity in neoplastic cell, myeloid cell and T cell populations that co-exist within VS, determining that the cellular composition of VS tumours is independent of NF2-SWN genetic severity. We show that distinct myeloid cell and Schwann cell populations exist within varied spatial contextures across characteristic Antoni A and B histomorphic niches. Interestingly, we show that T-cell populations associate with tumour-associated macrophages (TAMs) in Antoni A regions, seemingly limiting their ability to interact with tumorigenic Schwann cells. This spatial landscape is altered in Antoni B regions, where T-cell populations appear to interact with PD-L1+ Schwann cells. We also demonstrate that prior bevacizumab treatment (VEGF-A antagonist) preferentially reduces alternatively-activated TAMs, whilst enhancing CD44 expression, in bevacizumab-treated tumours. Together, we describe niche-dependent modes of T-cell regulation in NF2 SWN VS, indicating the potential for microenvironment-altering therapies for VS.

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“…However, this genetic predisposition alone does not entirely account for tumor biology, as not all VS tumors harbor NF2 mutations. Based on single-cell ribonucleic acid (RNA) sequencing, differential expression of merlin -regulated genes may also result in differential pathogenicity of NF2 mutations [ 33 ]. Genes unrelated to NF2 such as HGF/c-MET; noncoding genomes (such as microRNAs and epigenetic mechanisms) have also been implicated in sporadic VS.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Regression of a Large Vestibular Schwannoma: Is Nonoperative Management Reasonable?

Teo,

Agrwal,

Kei

et al. 2024

Brain Tumor Res Treat

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Vestibular schwannomas (VSs) are the most common cerebellopontine tumors. The natural history of smaller-sized VSs (<30 mm) has been well-studied, leading to the recommendation of a “watch and wait” approach. However, large VSs (>30 mm) have not been extensively studied, mainly because of their rarity. As such, most patients are conventionally offered surgery which carries a significant risk of neurological morbidity. Here, we report a case of a giant VS (>40 mm) in a 30-year-old man who regressed spontaneously. He was lost to follow-up for 18 years and, upon re-presentation, the symptomatology drastically improved and repeat imaging demonstrated a marked reduction in tumor size. Referring to similar cases in other studies, we postulate that most large and giant VSs undergo a phase of growth and stasis, followed by regression due to shifts in the balance between tumorigenic and regressive factors. Taken together with emerging molecular data, further studies are required to better understand the history of large and giant VSs to shape more personalized treatment options. This potentially includes non-operative management as a tenable option.

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Single-Cell RNA-Seq Reveals Heterogeneity of Cell Communications between Schwann Cells and Fibroblasts within Vestibular Schwannoma Microenvironment

Cited by 12 publications

References 78 publications

Single‐cell RNA‐seq uncovers novel metabolic functions of Schwann cells beyond myelination

Single‐cell RNA‐seq uncovers novel metabolic functions of Schwann cells beyond myelination

High-Dimensional Imaging of Vestibular Schwannoma Reveals Distinctive Immunological Networks Across Histomorphic Niches inNF2-related Schwannomatosis

Spontaneous Regression of a Large Vestibular Schwannoma: Is Nonoperative Management Reasonable?

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