Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse

Li, Yaqian; Zhang, Qingyang; Sun, Bao‐Fa; Ma, Yang; Zhang, Ye; Wang, Min; Ma, Congcong; Shi, Honghui; Sun, Zhijing; Chen, Juan; Yang, Yun‐Gui

doi:10.1038/s41467-020-20358-y

Cited by 53 publications

(47 citation statements)

References 56 publications

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“…SCENIC is a method for reconstructing gene regulatory networks and identifying stable cell states from scRNA-seq data ( 44 ). Transcription factor (TF) activity was calculated using SCENIC (version 1.1.3), as described previously ( 45 ). A read count matrix was inputted, with the cell types represented as columns and gene symbols shown in rows.…”

Section: Methodsmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

et al. 2021

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Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

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Section: Methodsmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

et al. 2021

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“…Therefore, we hypothesized that this clonogenic cell population of the cervix may be the stem/progenitor cells of the cervix, like their counterparts in other epithelial tissues and organs. To gain further insights into the features and behaviors of these putative stem/progenitor cells in vivo, the single-cell RNA-seq approach, which was frequently used to identify novel cell types or dissected cell heterogeneity within a ‘homogenous’ cell population (Wen and Tang 2016 ) in female reproductive system such as uterus (Wu et al 2017 ), cervix (Chumduri et al 2021 ) and vagina (Li et al 2021 ), was also applied.…”

Section: Introductionmentioning

confidence: 99%

Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium

Zhao

Wang

et al. 2021

Cell Regen

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Information about the dynamic change and post-injury regeneration of cervical epithelium is relatively rare, even though it is tightly related to gynecologic malignancy. Here, using a feeder cell-based culturing system, we stably cloned mouse and human P63 and KRT5 expressing cells from the adult cervix as putative cervical stem/progenitor cells (CVSCs). When subjected to differentiation, the cultured cells gave rise to mature cervical epithelium by differentiating into squamous or glandular cells. The ability of endogenous mouse CVSCs to reconstitute cervical epithelium after injury was also evident from the genetic lineage tracing experiments. Single-cell transcriptomic analysis further classified the CVSCs into three subtypes and delineated their bi-lineage differentiation roadmap by pseudo-time analysis. We also tracked the real-time differentiation routes of two representing single CVSC lines in vitro and found that they recapitulated the predicted roadmap in pseudo-time analysis. Signaling pathways including Wnt, TGF-beta, Notch and EGFR were found to regulate the cervical epithelial hierarchy and implicated the different roles of distinct types of cells in tissue homeostasis and tumorigenesis. Collectively, the above data provide a cloning system to achieve stable in vitro culture of a bi-lineage stem/progenitor cell population in the cervix, which has profound implications for our understanding of the cervix stem/progenitor cell function in homeostasis, regeneration, and disease and could be helpful for developing stem cell-based therapies in future.

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“…SCENIC is a suitable method for using transcription factors (TFs) to guide the discovery of cellular states from scRNA-seq data ( 15 ). The R package for SCENIC (version 1.2.4) was used as previously described to perform a transcription factor network inference analysis ( 16 ). Briefly, a read-count matrix from the Seruat S4 object was inputted.…”

Section: Methodsmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

Feng

Jiang

et al. 2021

Front. Oncol.

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Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

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Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse

Cited by 53 publications

References 56 publications

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

Single-cell analysis defines the lineage plasticity of stem cells in cervix epithelium

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

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