دورية أكاديمية
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Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.

التفاصيل البيبلوغرافية
العنوان: Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.
المؤلفون: McLean DT; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, United States.; Molecular & Environmental Toxicology Program, University of Wisconsin-Madison, Madison, WI, United States., Meudt JJ; Biomedical & Genomic Research Group, Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States., Lopez Rivera LD; Molecular & Environmental Toxicology Program, University of Wisconsin-Madison, Madison, WI, United States., Schomberg DT; Biomedical & Genomic Research Group, Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States., Pavelec DM; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, United States., Duellman TT; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, United States., Buehler DG; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States., Schwartz PB; Molecular & Environmental Toxicology Program, University of Wisconsin-Madison, Madison, WI, United States.; Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States., Graham M; Research Animal Resources and Compliance (RARC), Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison, Madison, WI, United States., Lee LM; Research Animal Resources and Compliance (RARC), Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison, Madison, WI, United States., Graff KD; Swine Research and Teaching Center, Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States., Reichert JL; Swine Research and Teaching Center, Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States., Bon-Durant SS; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, United States., Konsitzke CM; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, United States., Ronnekleiv-Kelly SM; Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States., Shanmuganayagam D; Molecular & Environmental Toxicology Program, University of Wisconsin-Madison, Madison, WI, United States.; Biomedical & Genomic Research Group, Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States.; Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.; Center for Biomedical Swine Research and Innovation, University of Wisconsin-Madison, Madison, WI, United States., Rubinstein CD; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, United States.
المصدر: Frontiers in oncology [Front Oncol] 2023 Sep 25; Vol. 13, pp. 1253659. Date of Electronic Publication: 2023 Sep 25 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مستخلص: Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely but nearly always include the development of cutaneous, plexiform and diffuse neurofibromas that are managed over many years. Recent single-cell transcriptomics profiling efforts of neurofibromas have begun to reveal cell signaling processes. However, the cell signaling networks in mature, non-cutaneous neurofibromas remain unexplored. Here, we present insights into the cellular composition and signaling within mature neurofibromas, contrasting with normal adjacent tissue, in a porcine model of NF1 using single-cell RNA sequencing (scRNA-seq) analysis and histopathological characterization. These neurofibromas exhibited classic diffuse-type histologic morphology and expected patterns of S100, SOX10, GFAP, and CD34 immunohistochemistry. The porcine mature neurofibromas closely resemble human neurofibromas histologically and contain all known cellular components of their human counterparts. The scRNA-seq confirmed the presence of all expected cell types within these neurofibromas and identified novel populations of fibroblasts and immune cells, which may contribute to the tumor microenvironment by suppressing inflammation, promoting M2 macrophage polarization, increasing fibrosis, and driving the proliferation of Schwann cells. Notably, we identified tumor-associated IDO1 + /CD274 + ( PD-L1) + dendritic cells, which represent the first such observation in any NF1 animal model and suggest the role of the upregulation of immune checkpoints in mature neurofibromas. Finally, we observed that cell types in the tumor microenvironment are poised to promote immune evasion, extracellular matrix reconstruction, and nerve regeneration.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 McLean, Meudt, Lopez Rivera, Schomberg, Pavelec, Duellman, Buehler, Schwartz, Graham, Lee, Graff, Reichert, Bon-Durant, Konsitzke, Ronnekleiv-Kelly, Shanmuganayagam and Rubinstein.)
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معلومات مُعتمدة: P30 CA014520 United States CA NCI NIH HHS; T32 ES007015 United States ES NIEHS NIH HHS
فهرسة مساهمة: Keywords: cancer-associated fibroblasts (CAF); immune checkpoint; neurofibroma; neurofibromatosis type 1 (NF1); neuroregeneration; single cell RNA seq; swine; tumor microenvironment (TME)
تواريخ الأحداث: Date Created: 20231011 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10561395
DOI: 10.3389/fonc.2023.1253659
PMID: 37817770
قاعدة البيانات: MEDLINE
الوصف
تدمد:2234-943X
DOI:10.3389/fonc.2023.1253659