Tumor-associated Schwann cells Expressing LncRNAs Direct Immune Resistant Metabolic Microenvironment
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ABSTRACT:
PROVIDER: PRJNA720086 | ENA |
REPOSITORIES: ENA
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Project description:Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues were performed. Results suggested that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrated that Schwann cells enhanced the proliferation and migration of PDAC cells via Midkine and promoted the switch of CAFs to iCAFs via interleukin-1a. By Schwann cells condition medium, tumor cells together with iCAFs accelerate PDAC progression. Thus, we revealed, for the first time, that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.
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Project description:Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues were performed. Results suggested that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrated that Schwann cells enhanced the proliferation and migration of PDAC cells via Midkine and promoted the switch of CAFs to iCAFs via interleukin-1a. By Schwann cells condition medium, tumor cells together with iCAFs accelerate PDAC progression. Thus, we revealed, for the first time, that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.
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Project description:Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs), a dermally-derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally-derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from facial (neural crest-derived) and foreskin (mesodermally-derived) dermis, and the mesodermally-derived SKPs can make myelinating Schwann cells. Thus, non-neural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally-defined lineage boundaries are more flexible than widely thought. We obtained 4 independent samples of neonatal human foreskin and 4 independent samples of discarded facial skin tissue from children less than two years old. Primary cells were isolated and cultured as SKPs and RNA was collected from those cultured samples. RNA samples deriving from these cells were analyzed on the Affymetrix Human Gene 2.0 ST Array.
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