المؤلفون: Wei Ge, Yuan-Chao Sun, Tian Qiao, Hai-Xia Liu, Tao-Ran He, Jun-Jie Wang, Chun-Lei Chen, Shun-Feng Cheng, Paul W. Dyce, Massimo De Felici, Wei Shen

المصدر: Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-13 (2023)

مصطلحات موضوعية: Skin-derived stem cells, Papillary dermal fibroblast progenitors, Single-cell transcriptomes, Spermatogonial stem cells like cells, Medicine (General), R5-920, Biochemistry, QD415-436

الوصف: Abstract Background Many laboratories have described the in vitro isolation of multipotent cells with stem cell properties from the skin of various species termed skin-derived stem cells (SDSCs). However, the cellular origin of these cells and their capability to give rise, among various cell types, to male germ cells, remain largely unexplored. Methods SDSCs were isolated from newborn mice skin, and then differentiated into primordial germ cell-like cells (PGCLCs) in vitro. Single-cell RNA sequencing (scRNA-seq) was then applied to dissect the cellular origin of SDSCs using cells isolated from newborn mouse skin and SDSC colonies. Based on an optimized culture strategy, we successfully generated spermatogonial stem cell-like cells (SSCLCs) in vitro. Results Here, using scRNA-seq and analyzing the profile of 7543 single-cell transcriptomes from newborn mouse skin and SDSCs, we discovered that they mainly consist of multipotent papillary dermal fibroblast progenitors (pDFPs) residing in the dermal layer. Moreover, we found that epidermal growth factor (EGF) signaling is pivotal for the capability of these progenitors to proliferate and form large colonies in vitro. Finally, we optimized the protocol to efficiently generate PGCLCs from SDSCs. Furthermore, PGCLCs were induced into SSCLCs and these SSCLCs showed meiotic potential when cultured with testicular organoids. Conclusions Our findings here identify pDFPs as SDSCs derived from newborn skin and show for the first time that such precursors can be induced to generate cells of the male germline.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1757-6512Test

الوصول الحر: https://doaj.org/article/1a3e7537a5d643ddb56fd0e6402517f7Test

المؤلفون: Tao Yang, Qiyu Yan, Rongzhuo Long, Zhixian Liu, Xiaosheng Wang

المصدر: Computational and Structural Biotechnology Journal, Vol 21, Iss , Pp 3604-3614 (2023)

مصطلحات موضوعية: Ensemble learning algorithm, Single-cell transcriptomes, Cancer and non-cancer cells, Tumor marker genes, Non-tumor marker genes, Biotechnology, TP248.13-248.65

الوصف: We propose PreCanCell, a novel algorithm for predicting malignant and non-malignant cells from single-cell transcriptomes. PreCanCell first identifies the differentially expressed genes (DEGs) between malignant and non-malignant cells commonly in five common cancer types-associated single-cell transcriptome datasets. The five common cancer types include renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), melanoma, lung adenocarcinoma (LUAD), and breast cancer (BC). With each of the five datasets as the training set and the DEGs as the features, a single cell is classified as malignant or non-malignant by k-NN (k = 5). Finally, the single cell is determined as malignant or non-malignant by the majority vote of the five k-NN classification results. We tested the predictive performance of PreCanCell in 19 single-cell datasets, and reported classification accuracy, sensitivity, specificity, balanced accuracy (the average of sensitivity and specificity) and the area under the receiver operating characteristic curve (AUROC). In all these datasets, PreCanCell achieved above 0.8 accuracy, sensitivity, specificity, balanced accuracy and AUROC. Finally, we compared the predictive performance of PreCanCell with that of seven other algorithms, including CHETAH, SciBet, SCINA, scmap-cell, scmap-cluster, SingleR, and ikarus. Compared to these algorithms, PreCanCell displays the advantages of higher accuracy and simpler implementation. We have developed an R package for the PreCanCell algorithm, which is available at https://github.com/WangX-Lab/PreCanCellTest.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S200103702300243XTest; https://doaj.org/toc/2001-0370Test

الوصول الحر: https://doaj.org/article/1310ef1906d74fbf8481b1029b8bf26aTest

المؤلفون: Ge, Wei, Sun, Yuan-Chao, Qiao, Tian, Liu, Hai-Xia, He, Tao-Ran, Wang, Jun-Jie, Chen, Chun-Lei, Cheng, Shun-Feng, Dyce, Paul W, De Felici, Massimo, Shen, Wei

المساهمون: Ge, W, Sun, Y, Qiao, T, Liu, H, He, T, Wang, J, Chen, C, Cheng, S, Dyce, Pw, De Felici, M, Shen, W

مصطلحات موضوعية: Papillary dermal fibroblast progenitors, Single-cell transcriptomes, Skin-derived stem cells, Spermatogonial stem cells like cells, Settore BIO/17 - ISTOLOGIA

الوصف: BackgroundMany laboratories have described the in vitro isolation of multipotent cells with stem cell properties from the skin of various species termed skin-derived stem cells (SDSCs). However, the cellular origin of these cells and their capability to give rise, among various cell types, to male germ cells, remain largely unexplored.MethodsSDSCs were isolated from newborn mice skin, and then differentiated into primordial germ cell-like cells (PGCLCs) in vitro. Single-cell RNA sequencing (scRNA-seq) was then applied to dissect the cellular origin of SDSCs using cells isolated from newborn mouse skin and SDSC colonies. Based on an optimized culture strategy, we successfully generated spermatogonial stem cell-like cells (SSCLCs) in vitro.ResultsHere, using scRNA-seq and analyzing the profile of 7543 single-cell transcriptomes from newborn mouse skin and SDSCs, we discovered that they mainly consist of multipotent papillary dermal fibroblast progenitors (pDFPs) residing in the dermal layer. Moreover, we found that epidermal growth factor (EGF) signaling is pivotal for the capability of these progenitors to proliferate and form large colonies in vitro. Finally, we optimized the protocol to efficiently generate PGCLCs from SDSCs. Furthermore, PGCLCs were induced into SSCLCs and these SSCLCs showed meiotic potential when cultured with testicular organoids.ConclusionsOur findings here identify pDFPs as SDSCs derived from newborn skin and show for the first time that such precursors can be induced to generate cells of the male germline.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36737797; info:eu-repo/semantics/altIdentifier/wos/WOS:000925966200001; volume:14; issue:1; firstpage:17; journal:STEM CELL RESEARCH & THERAPY; https://hdl.handle.net/2108/330563Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85147422483

الإتاحة: https://doi.org/10.1186/s13287-023-03243-5Test
https://hdl.handle.net/2108/330563Test

المؤلفون: Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Timmermann, Bernd, Bossini-Castillo, L., Martin, Javier, Klages, Sven

المساهمون: Junta de Andalucía, Ministerio de Ciencia e Innovación (España), FONDOS FEDER, Instituto de Salud Carlos III

مصطلحات موضوعية: Systemic sclerosis, Single-cell transcriptomes, cRNA-seq, Monocyte, CD14

الوصف: Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in the peripheral blood (PB). PB monocytes (Mos) are recruited into tissues where they differentiate into macrophages, which are directly involved in fibrosis. To understand the role of CD14+ PB Mos in SSc, a single-cell transcriptome analysis (scRNA-seq) was conducted on 8 SSc patients and 8 controls. Using unsupervised clustering methods, CD14+ cells were assigned to 11 clusters, which added granularity to the known monocyte subsets: classical (cMos), intermediate (iMos) and non-classical Mos (ncMos) or type 2 dendritic cells. NcMos were significantly overrepresented in SSc patients and showed an active IFN-signature and increased expression levels of PTGES, in addition to monocyte motility and adhesion markers. We identified a SSc-related cluster of IRF7+ STAT1+ iMos with an aberrant IFN-response. Finally, a depletion of M2 polarised cMos in SSc was observed. Our results highlighted the potential of PB Mos as biomarkers for SSc and provided new possibilities for putative drug targets for modulating the innate immune response in SSc. ; This work was supported by the grant P18-RT-4442 funded by Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía. “Red de Investigación Cooperativa Orientada a Resultados en Salud'' (RICOR, RD21/0002/003). 115565. LBC was supported by the Spanish Ministry of Science and Innovation through the Juan de la Cierva Incorporación' program (Grant ref. IJC2018-038026-I, funded by MCIN/AEI/10.13039/501,100,011,033), which includes FEDER funds. MAH is a recipient of a Miguel Servet fellowship (CP21/00132) from the Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation). GV-M was funded by the Grant PRE2019-087586 funded by MCIN/AEI/10.13039/501,100,011,033 and by “ESF Investing in your future”.

العلاقة: Publisher's version; http://dx.doi.org/10.1016/j.jaut.2023.103097Test; Sí; Journal of Autoimmunity 140: 103097 (2023); http://hdl.handle.net/10261/354839Test

الإتاحة: https://doi.org/10.1016/j.jaut.2023.103097Test
http://hdl.handle.net/10261/354839Test

المؤلفون: Hua-Ping Liu, Dongwen Wang, Hung-Ming Lai

المصدر: Computational and Structural Biotechnology Journal, Vol 20, Iss , Pp 2672-2679 (2022)

مصطلحات موضوعية: Single cell transcriptomes, Circulating tumor cells, RNA-seq, Translational bioinformatics, Digit medicine, Biotechnology, TP248.13-248.65

الوصف: There is a growing need to build a model that uses single cell RNA-seq (scRNA-seq) to separate malignant cells from nonmalignant cells and to identify tumor of origin of single cells and/or circulating tumor cells (CTCs). Currently, it is infeasible to build a tumor of origin model learnt from scRNA-seq by machine learning (ML). We then wondered if an ML model learnt from bulk transcriptomes is applicable to scRNA-seq to infer single cells’ tumor presence and further indicate their tumor of origin. We used k-nearest neighbors, one-versus-all support vector machine, one-versus-one support vector machine, random forest and introduced scTumorTrace to conduct a pioneering experiment containing leukocytes and seven major cancer types where bulk RNA-seq and scRNA-seq data were available. 13 ML models learnt from bulk RNA-seq were all reliable to use (F-score > 96%) shown by a validation set of bulk transcriptomes, but none of them was applicable to scRNA-seq except scTumorTrace. Making inferences from bulk RNA-seq to scRNA-seq was impaired by feature selection and improved by log2-transformed TPM units. scTumorTrace with transcriptome-wide 2-tuples showed F-score beyond 98.74 and 94.29% in inferring tumor presence and tumor of origin at single-cell resolution and correctly identified 45 single candidate prostate CTCs but lineage-confirmed non-CTCs as leukocytes. We concluded that modern ML techniques are quantitative and could hardly address the raised questions. scTumorTrace with transcriptome-wide 2-tuples is qualitative, standardization-free and not subject to log2-transformed quantities, enabling us to infer tumor presence of single cell transcriptomes and their tumor of origin from bulk transcriptomes.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S200103702200191XTest; https://doaj.org/toc/2001-0370Test

الوصول الحر: https://doaj.org/article/e9d0dca5838f4c37bf87d4985ec8c43cTest

المؤلفون: Wu-lin Zuo, Mahboubeh R. Rostami, Shushila A. Shenoy, Michelle G. LeBlanc, Jacqueline Salit, Yael Strulovici-Barel, Sarah L. O’Beirne, Robert J. Kaner, Philip L. Leopold, Jason G. Mezey, Juergen Schymeinsky, Karsten Quast, Sudha Visvanathan, Jay S. Fine, Matthew J. Thomas, Ronald G. Crystal

المصدر: Respiratory Research, Vol 21, Iss 1, Pp 1-11 (2020)

مصطلحات موضوعية: Single-cell transcriptomes, Epithelial cells, Immune/inflammatory cells, Inherited and acquired pulmonary disorders, Cigarette smoking, Diseases of the respiratory system, RC705-779

الوصف: Abstract Background The human small airway epithelium (SAE) plays a central role in the early events in the pathogenesis of most inherited and acquired lung disorders. Little is known about the molecular phenotypes of the specific cell populations comprising the SAE in humans, and the contribution of SAE specific cell populations to the risk for lung diseases. Methods Drop-seq single-cell RNA-sequencing was used to characterize the transcriptome of single cells from human SAE of nonsmokers and smokers by bronchoscopic brushing. Results Eleven distinct cell populations were identified, including major and rare epithelial cells, and immune/inflammatory cells. There was cell type-specific expression of genes relevant to the risk of the inherited pulmonary disorders, genes associated with risk of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis and (non-mutated) driver genes for lung cancers. Cigarette smoking significantly altered the cell type-specific transcriptomes and disease risk-related genes. Conclusions This data provides new insights into the possible contribution of specific lung cells to the pathogenesis of lung disorders.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12931-020-01442-9Test; https://doaj.org/toc/1465-993XTest

الوصول الحر: https://doaj.org/article/af8f66ce0af64a4dbed6220fd72ca500Test

المؤلفون: Gennaro Gambardella

مصطلحات موضوعية: Genomics and transcriptomics, Pharmacogenomics, single cell transcriptomes, drug sensitivity datasets

الوصف: Drug response prediction at the single-cell level is an emerging field of research that aims to improve the efficacy and precision of cancer treatments. Here, we introduce DREEP(Drug Response Estimation from single-cell Expression Profiles), a computational method that leverages publicly available pharmacogenomic screens and functional enrichment analysis to predict single-cell drug sensitivity from transcriptomic data. We validated DREEP extensively in Vitro using several independent single-cell datasets with over 200 cancer cell lines and showed its accuracy and robustness. Additionally, we also applied DREEP to molecularly barcoded breast cancer cells and identified drugs that can selectively target specific cell populations. DREEP provides an in-silico framework to prioritize drugs from single-cell transcriptional profiles of tumours and thus helps in designing personalized treatment strategies and accelerating drug repurposing studies. DREEP is available at https://github.com/gambalab/DREEPTest .

العلاقة: https://figshare.com/articles/dataset/Predicting_drug_response_from_single-cell_expression_profiles_DREEP_/23261234Test

الإتاحة: https://doi.org/10.6084/m9.figshare.23261234.v1Test
https://figshare.com/articles/dataset/Predicting_drug_response_from_single-cell_expression_profiles_DREEP_/23261234Test

المؤلفون: Tomas Panek

مصطلحات موضوعية: Microbial taxonomy, Phylogeny and comparative analysis, Phylogenomics, Genetic code evolution, Tropidoatractidae, Palmarella, single cell transcriptomes, anaerobic ciliate

الوصف: 18S rRNA dataset single-gene datasets for phylogenomics detected contaminant sequences and paralogs concatenated phylogenomic matrices transcriptome assemblies of newly sequenced taxa (cleaned by WinstonCleaner) datasets used for analysis of stop codon identity in APM ciliates datasets of identified 3´UTRs and mapped CDS onto respective transcriptomic contigs output file of codetta

العلاقة: https://figshare.com/articles/dataset/Data_sets_used_in_the_manuscript_Single_cell_transcriptomics_reveals_UAR_codon_reassignment_in_Palmarella_salina_Metopida_Armophorea_and_confirms_Armophorida_belongs_to_APM_clade_/24717990Test

الإتاحة: https://doi.org/10.6084/m9.figshare.24717990.v1Test
https://figshare.com/articles/dataset/Data_sets_used_in_the_manuscript_Single_cell_transcriptomics_reveals_UAR_codon_reassignment_in_Palmarella_salina_Metopida_Armophorea_and_confirms_Armophorida_belongs_to_APM_clade_/24717990Test

المؤلفون: Richard Poulsom, Hartmut Koeppen, Philip J. Coates, C. Simon Herrington

المصدر: Herrington, C S, Poulsom, R, Koeppen, H & Coates, P J 2021, ' Recent Advances in Pathology: the 2021 Annual Review Issue of The Journal of Path ', Journal of Pathology . https://doi.org/10.1002/path.5687Test

مصطلحات موضوعية: mitochondrial pathology, Pathology, Research areas, Disease, migration, chromatin modification, 0302 clinical medicine, HDAC inhibitors, oncogene, severe actute reisparatory syndrome coronovirus 2 (SARS-CoV-2), therapeutic discovery, tumour microenviroment, GWAS, genetics, tumour-infiltrating lymphocytes, pathophysiology, Smad, spatial transcriptomics, local microbiota, Respiratory infection, Genomics, Biobank, macrophages, Organoids, mitochondrial disease, imilimumab, 030220 oncology & carcinogenesis, nephroblastoma, pembrolizumab, stretch, atezolizumab, medicine.medical_specialty, cancer stem cells (CSCs), mouse model, human genetics, shear stress, Pathology and Forensic Medicine, TGF-B, genetic diagnosis, 03 medical and health sciences, proteomics, MDM2, stem cells, squamous cell cancer, genomics, Humans, Subject areas, single cell transcriptomes, microbial toxins, nivolumab, gene enhancers, mmunopathology, cellular crosstalk, Precision medicine, MAPK, ioiopathic pulmonary birosis, 030104 developmental biology, CSC niche, soft tissue, p53, 0301 basic medicine, microbial metabolites, History, multiplex immunohistochemistry, sarcome, microbiome, bone, stiffness, Neoplasms, profibrotic, TIF1beta, epithelial to mesenchymal transition (EMT), Wilms' tumour, organoids, p63, treatment, autoimmunity, phagocytosis, dysbiosis, intratumoral microbiota, metabolomics, humanities, inflmamation, acute resiparatory distress syndrome (ARDS), KAP1, mTOR, immunotherapy, 3D culture, PD-L1, tumour suppressor, extracellular matrix, precision medicine, microstructure, cancer predisposition, PD01, Translational research, medicine, cancer, angiotensin-converting enzyme 2 (ACE2), damage-associated molecular patterns, immuno-oncology, polarization, therapy, endothelial to mesenchymal transition (endMT), epigenetics, SARS-CoV-2, TRIM28, antifibrotic, COVID-19, cell of origin, cancer progression, United Kingdom, multiplex in situe hybridization, Transplantation, tumorigenesis, polygenic risk score, IL-33, pathology, coronavirus diseas 2019 (COVID-19)

الوصف: The 2021 Annual Review Issue of The Journal of Pathology contains 14 invited reviews on current research areas of particular importance in pathology. The subjects included here reflect the broad range of interests covered by the journal, including both basic and applied research fields but always with the aim of improving our understanding of human disease. This year, our reviews encompass the huge impact of the COVID-19 pandemic, the development and application of biomarkers for immune checkpoint inhibitors, recent advances in multiplexing antigen/nucleic acid detection in situ, the use of genomics to aid drug discovery, organoid methodologies in research, the microbiome in cancer, the role of macrophage-stroma interactions in fibrosis, and TGF-β as a driver of fibrosis in multiple pathologies. Other reviews revisit the p53 field and its lack of clinical impact to date, dissect the genetics of mitochondrial diseases, summarise the cells of origin and genetics of sarcomagenesis, provide new data on the role of TRIM28 in tumour predisposition, review our current understanding of cancer stem cell niches, and the function and regulation of p63. The reviews are authored by experts in their field from academia and industry, and provide comprehensive updates of the chosen areas, in which there has been considerable recent progress. © 2021 The Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5a2683cce62a47fe3c9c1c3a6cdb89aTest
https://doi.org/10.1002/path.5687Test

المؤلفون: Cheng, Qing, Butler, William, Zhou, Yinglu, Zhang, Hong, Tang, Lu, Perkinson, Kathryn, Chen, Xufeng, Jiang, Xiaoyin Sara, McCall, Shannon J, Inman, Brant A, Huang, Jiaoti

مصطلحات موضوعية: Castration-resistant prostate cancer, Castration-resistant prostate cancer–like cells, Critical transcription regulator, Evolutionary trajectory, Intratumor heterogeneity, Large population validation, Neuroendocrine differentiation, Primary prostate cancer, Single-cell transcriptomes

الوصف: Background Hormonal therapy targeting the androgen receptor inhibits prostate cancer (PCa), but the tumor eventually recurs as castration-resistant prostate cancer (CRPC). Objective To understand the mechanisms by which subclones within early PCa develop into CRPC. Design, setting, and participants We isolated epithelial cells from fresh human PCa cases, including primary adenocarcinoma, locally recurrent CRPC, and metastatic CRPC, and utilized single-cell RNA sequencing to identify subpopulations destined to become either CRPC-adeno or small cell neuroendocrine carcinoma (SCNC). Outcome measurements and statistical analysis We revealed dynamic transcriptional reprogramming that promotes disease progression among 23226 epithelial cells using single-cell RNA sequencing, and validated subset-specific progression using immunohistochemistry and large cohorts of publically available genomic data. Results and limitations We identified a small fraction of highly plastic CRPC-like cells in hormone-naïve early PCa and demonstrated its correlation with biochemical recurrence and distant metastasis, independent of clinical characteristics. We show that progression toward castration resistance was initiated from subtype-specific lineage plasticity and clonal expansion of pre-existing neuroendocrine and CRPC-like cells in early PCa. Conclusions CRPC-like cells are present early in the development of PCa and are not exclusively the result of acquired evolutionary selection during androgen deprivation therapy. The lethal CRPC and SCNC phenotypes should be targeted earlier in the disease course of patients with PCa. Patient summary Here, we report the presence of pre-existing castration-resistant prostate cancer (CRPC)-like cells in primary prostate cancer, which represents a novel castration-resistant mechanism different from the adaptation mechanism after androgen deprivation therapy (ADT). Patients whose tumors harbor increased pre-existing neuroendocrine and CRPC-like cells may become rapidly resistant to ADT and may ...

وصف الملف: application/pdf

العلاقة: European urology; S0302-2838(22)00001-X; https://hdl.handle.net/10161/24260Test

الإتاحة: https://hdl.handle.net/10161/24260Test