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Series GSE135851 Query DataSets for GSE135851
Status Public on Jul 11, 2020
Title Identification of the lymphangioleiomyomatosis cell and its uterine origin
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Lymphangioleiomyomatosis (LAM) is a metastasizing neoplasm of reproductive age women which causes cystic lung remodeling and progressive respiratory failure. While LAM lesions are known to contain abnormal smooth muscle-like cells which harbor mTOR activating mutations in TSC1 or TSC2, the tissue origins of the mutant “LAM cells” that invade the lung remain unclear. By employing single cell and single nuclear RNA sequencing on explanted LAM lungs, we identified a unique population of cells and associated signature genes and gene networks which were readily distinguished from those of endogenous lung cells. These unique LAMCORE cells shared closest transcriptomic similarity to normal uterus and share transcriptomic features with neural crest, as identified in uterine LAM lesions by single nuclear RNA-seq. Immunofluorescence microscopy demonstrated the expression of LAMCORE cell signature genes within LAM lesions in both lung and uterus. Serum aptamer proteomics and ELISA identified biomarkers consistent with the signature genes expressed and predicted to be secreted by LAMCORE cells. Single cell transcriptomics strongly supports a uterine neural crest origin of LAMCORE cells; providing insights into disease pathogenesis and informing future treatment strategies for LAM.
Overall design scRNA-seq and snRNA-seq was performed using the 10x Chromium platform on four lung explants from LAM patients undergoing lung transplantation. We also performed scRNA-seq on a renal AML resected from a patient with a sporadic AML (S-AML), and snRNA-seq on uterine tissue obtained at hysterectomy from an S-LAM patient. As controls, we conducted scRNA-seq on a 31 years old female explanted lung, brain dead, beating-heart, organ donor and snRNA-seq on one normal uterine tissue at hysterectomy from a 29 years old female patient with cervical cancer, and obtained scRNA-seq data of six additional female donor lungs from Gene Expression Omnibus (GSE122960) and scRNA-seq data from normal mouse uterus (GSE118180). qRT-PCR, immunofluorescence and immunochemical stains to validate the spatial relationships of LAM cells and LAMCORE signature genes.Serum aptamer proteomics and ELISA assays screening were used for validation of secretome predictions.
Contributor(s) Guo M, Xu Y, McCormack FX, Whitsett J, Yu J, Perl AK, Wikenheiser-Brokamp KA, Potter SS
Citation(s) 32603599
Submission date Aug 14, 2019
Last update date Jul 14, 2020
Contact name Yan Xu
Phone 513-6368921
Organization name Cincinnati Children's Hospital Medical Center
Street address 3333 Burnet Ave
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM4035465 LAM1
GSM4035466 LAM2
GSM4035467 LAM3
BioProject PRJNA560283
SRA SRP218388

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Supplementary file Size Download File type/resource
GSE135851_RAW.tar 603.9 Mb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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