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| Status |
Public on May 01, 2024 |
| Title |
KMT2A-driven cyclin D2 upregulation and chronic inflammation as potential drivers of sporadic parathyroid adenoma pathogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, but the mechanisms involved in its pathogenesis remain incompletely understood. Here we present a single-cell transcriptomic atlas detailing the cellular differences between human PA and normal parathyroid gland (PG) tissues and delineating the transcriptome of individual cell types. We show that there is a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells (PGCs), with transcriptional upregulation of cyclin D2 driven by the transcriptional coactivator, histone-lysine N-methyltransferase 2A (KMT2A) through the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3) potentially involved in promoting PAC proliferation. Moreover, we demonstrate that PA tissues are heavily infiltrated with myeloid cells, and that fibroblasts, endothelial cells (ECs), as well as macrophages in the PA microenvironment are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. Collectively, these results provide new insights into the etiology of PA, where the pathogenesis likely involves the net contribution of the dysregulated KMT2A-STAT3/GATA3-cyclin D2 axis in PACs and the chronic inflammation of the microenvironment. These findings provide practical implications for the treatment of PA through KMT2A targeting and anti-inflammation therapies.
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| Overall design |
Five parathyroid glands of patients with sporadic parathyroid adenoma and three parathyroid glands of patients with Thyroid cancer
NOTE: Processed data file GSM8016804_ctrl1-matrix.mtx.gz is corrupt. The submitter has been contacted.
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| Contributor(s) |
Xu Q, La T, Wang L, Zhang XD, Shao F, Cao H |
| Citation(s) |
38888967 |
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| Submission date |
Dec 13, 2021 |
| Last update date |
Dec 09, 2024 |
| Contact name |
Ting La |
| E-mail(s) |
ting.la@uon.edu.au
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| Phone |
49217970
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| Organization name |
UON
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| Street address |
University Drive
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| City |
Callaghan |
| State/province |
NSW |
| ZIP/Postal code |
2308 |
| Country |
Australia |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA788456 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190773_RAW.tar |
237.3 Mb |
(http)(custom) |
TAR (of MTX, TSV, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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