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| Status |
Public on Apr 19, 2020 |
| Title |
Transcriptomic changes in response to modulation of long-non-coding RNA, LINC00473 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, LINC00473 which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. LINC00473 is detected in progenitor cells, and increases upon differentiation and in response to cAMP. In contrast to other known adipocyte LincRNAs, LINC00473 shuttles out of the nucleus, colocalizes and can be crosslinked to mitochondrial and lipid droplet proteins. Up- or down- regulation of LINC00473 results in reciprocal alterations in lipolysis, respiration and transcription of genes associated with mitochondrial oxidative metabolism. Depletion of PLIN1 results in impaired cAMP-responsive LINC00473 expression and lipolysis, indicating bidirectional interactions between PLIN1, LINC00473 and mitochondrial oxidative functions. Thus, we suggest that LINC00473 is a key regulator of human thermogenic adipocyte function, and reveals a role for a LincRNA in inter-organelle communication and human energy metabolism.
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| Overall design |
To fully understand the functional consequences of LINC00473-mediated modulation of mitochondrial respiration and lipolysis, we analyzed the transcriptome of adipocytes derived from human subcutaneous adipose derived progenitor cells overexpressing LINC00473, and that of cells in which LINC00473 expression was blunted with siRNA.
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| Contributor(s) |
Tran K, Brown EL, DeSouza T, Jespersen NZ, Nandrup-Bus C, Yang Q, Yang Z, Desai A, Min S, Rojas-Rodriguez R, Lundh M, Feizi A, Willenbrock H, Larsen TJ, Severinsen MC, Malka K, Mozzicato AM, Deshmukh AS, Emanuelli B, Pedersen BK, Fitzgibbons T, Scheele C, Corvera S, Nielsen S |
| Citation(s) |
32440655 |
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| Submission date |
Apr 18, 2020 |
| Last update date |
Jul 19, 2020 |
| Contact name |
Silvia Corvera |
| E-mail(s) |
silvia.corvera@umassmed.edu
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| Organization name |
University of Massachusetts Medical School
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| Street address |
373 Plantation St
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| City |
Worcester |
| ZIP/Postal code |
01605 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA626376 |
| SRA |
SRP257261 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148896_TPM.txt.gz |
935.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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