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Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks

Akerman, Ildem ; Tu, Zhidong ; Beucher, Anthony ; Rolando, Delphine M Y ; Sauty-Colace, Claire ; Benazra, Marion ; Nakic, Nikolina ; Yang, Jialiang ; Wang, Huan L. and Pasquali, Lorenzo , et al. (2017) In Cell Metabolism 25(2). p.400-411
Abstract

Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D... (More)

Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chromatin, CRISPR interference, diabetes, lncRNAs, long noncoding RNAs, pancreatic islets, PDX1, PLUTO, transcriptional networks, type 2 diabetes
in
Cell Metabolism
volume
25
issue
2
pages
12 pages
publisher
Cell Press
external identifiers
  • pmid:28041957
  • wos:000396354400020
  • scopus:85009909783
ISSN
1550-4131
DOI
10.1016/j.cmet.2016.11.016
language
English
LU publication?
yes
id
28c0f789-ce8e-46e1-805b-d7d4a577fcfa
date added to LUP
2017-04-19 11:29:06
date last changed
2024-04-29 09:34:14
@article{28c0f789-ce8e-46e1-805b-d7d4a577fcfa,
  abstract     = {{<p>Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.</p>}},
  author       = {{Akerman, Ildem and Tu, Zhidong and Beucher, Anthony and Rolando, Delphine M Y and Sauty-Colace, Claire and Benazra, Marion and Nakic, Nikolina and Yang, Jialiang and Wang, Huan L. and Pasquali, Lorenzo and Moran, Ignasi and Garcia-Hurtado, Javier and Castro, Natalia and Gonzalez-Franco, Roser and Stewart, Andrew F. and Bonner, Caroline and Piemonti, Lorenzo and Berney, Thierry and Groop, Leif and Kerr-Conte, Julie and Pattou, Francois and Argmann, Carmen and Schadt, Eric and Ravassard, Philippe and Ferrer, Jorge}},
  issn         = {{1550-4131}},
  keywords     = {{chromatin; CRISPR interference; diabetes; lncRNAs; long noncoding RNAs; pancreatic islets; PDX1; PLUTO; transcriptional networks; type 2 diabetes}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{400--411}},
  publisher    = {{Cell Press}},
  series       = {{Cell Metabolism}},
  title        = {{Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks}},
  url          = {{http://dx.doi.org/10.1016/j.cmet.2016.11.016}},
  doi          = {{10.1016/j.cmet.2016.11.016}},
  volume       = {{25}},
  year         = {{2017}},
}