Imperial College London
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ProfessorBorisLenhard

Faculty of Medicine, Institute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 7594 0911b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

6.12CLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lopez-Noriega:2020:10.1101/2020.07.17.209015,
author = {Lopez-Noriega, L and Callingham, R and Martinez-Sánchez, A and Nawaz, S and Pizza, G and Haberman, N and Cvetesic, N and Nguyen-Tu, M-S and Lenhard, B and Marchetti, P and Piemonti, L and de, Koning E and Shapiro, AMJ and Johnson, PR and Leclerc, I and Hastoy, B and Gauthier, BR and Pullen, TJ and Rutter, GA},
doi = {10.1101/2020.07.17.209015},
title = {Roles for the long non-coding RNA<i>Pax6os1</i>/<i>PAX6-AS1</i>in pancreatic beta cell identity and function},
url = {http://dx.doi.org/10.1101/2020.07.17.209015},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:sec><jats:title>Aim/Hypothesis</jats:title><jats:p>Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell development and function. Here, we investigate roles for an antisense lncRNA expressed from the<jats:italic>Pax6</jats:italic>locus (annotated as<jats:italic>Pax6os1</jats:italic>in mice and<jats:italic>PAX6-AS1</jats:italic>in humans) in beta cell identity and functionality.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>Pax6os1</jats:italic>expression was silenced in MIN6 cells using siRNAs and changes in gene expression were determined by RNA sequencing or qRT-PCR. Mice inactivated for<jats:italic>Pax6os1</jats:italic>and human<jats:italic>PAX6-AS1</jats:italic>-null EndoC-βH1 cells, were generated using CRISPR/Cas9 technology. Human islets were infected with lentiviral vectors bearing a targeted shRNA or<jats:italic>PAX6-AS1</jats:italic>, which were used to silence or overexpress, respectively, the lncRNA. RNA sequencing or RT-qPCR were used to measure transcriptomic changes and RNA pulldown in mice and human cells followed by mass spectrometry/western blot were performed to explore RNA protein interactions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic>Pax6os1/PAX6-AS1</jats:italic>expression was upregulated at high glucose concentrations in derived beta cell lines as well as in mouse and human islets, and in pancreatic islets isolated from mice fed a high fat diet (n=6, p=0.003) and patients with type 2 diabetes (n=11-5, p<0.01). Silencing or deletion of<jats:italic>Pax6os1</jats:italic>/<jats:italic>PAX6-AS1</jats:italic>in MIN6 or EndoC-βH1cells increased the expression of several
AU  - Lopez-Noriega,L
AU  - Callingham,R
AU  - Martinez-Sánchez,A
AU  - Nawaz,S
AU  - Pizza,G
AU  - Haberman,N
AU  - Cvetesic,N
AU  - Nguyen-Tu,M-S
AU  - Lenhard,B
AU  - Marchetti,P
AU  - Piemonti,L
AU  - de,Koning E
AU  - Shapiro,AMJ
AU  - Johnson,PR
AU  - Leclerc,I
AU  - Hastoy,B
AU  - Gauthier,BR
AU  - Pullen,TJ
AU  - Rutter,GA
DO  - 10.1101/2020.07.17.209015
PY  - 2020///
TI  - Roles for the long non-coding RNA<i>Pax6os1</i>/<i>PAX6-AS1</i>in pancreatic beta cell identity and function
UR  - http://dx.doi.org/10.1101/2020.07.17.209015
ER  -
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