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| Status |
Public on Apr 03, 2023 |
| Title |
Integrative Single Cell Multiomic Profiling Analysis Reveals HOX-PBX Gene Regulatory Network Regulating the Survival of mTOR Hyperactive Cells [snRNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lymphangioleiomyomatosis (LAM) is a rare, debilitating lung disease that predominantly affects women of reproductive age. LAM cells carry deleterious mutations of tuberous sclerosis complex (TSC1/TSC2) genes, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) and ultimately dysregulated cell growth. The integrative single cell omics data identified the activation of uterine specific HOX-PBX transcriptional programming in pulmonary LAMCORE cells. Network analysis predicted homeobox transcription factors including PBX1 and HOXD11 as key regulators controlling LAMCORE cell fate. Targeting the HOX-PBX network may have therapeutic value in LAM and TSC-related diseases, and possibly in other mTORC1-hyperactive neoplasms.
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| Overall design |
In this study, we employed single cell/ single nuclei RNAseq and ATACseq data integration and gene regulatory network approach in conjunction with biochemical and functional assays using in vivo and in vitro LAM models to gain better understanding on molecular mechanisms responsible for the survival of LAM cells and inform the development of novel therapeutic targets for LAM.
Submitter states that raw data will be submitted to dbGap.
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| Contributor(s) |
Olatoke TF, Wagner A, Astrinidis AA, Guo M, Zhang EY, Zhang AG, Mattam U, Kopras EJ, Gupta N, Smith EP, Karbowniczek M, Markiewkski MM, Wikenheiser-Brokamp K, Whitsett JA, McCormack FX, Xu Y, Yu JJ |
| Citation(s) |
37163604 |
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| Submission date |
Nov 02, 2022 |
| Last update date |
Jul 05, 2023 |
| Contact name |
Yan Xu |
| E-mail(s) |
yan.xu@cchmc.org
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| Phone |
513-6368921
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| Organization name |
Cincinnati Children's Hospital Medical Center
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| Street address |
3333 Burnet Ave
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE217108 |
Integrative Single Cell Multiomic Profiling Analysis Reveals HOX-PBX Gene Regulatory Network Regulating the Survival of mTOR Hyperactive Cells |
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| Relations |
| BioProject |
PRJNA896957 |
