The long noncoding RNA MALAT1 predicts human pancreatic islet isolation quality

Wilson W.K. Wong, Guochi Jiang, Anja Elaine Sørensen, Yi Vee Chew, Cody Lee-Maynard, David Liuwantara, Lindy Williams, Phillip O'Connell, Louise Torp Dalgaard, Ronald C. Ma, Wayne J. Hawthorne, Mugdha Joglekar, Anandwardhan Awadhoot Hardikar

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Abstract

Human islet isolation is a cost-/resource-intensive program generating islets for cell therapy in Type 1 diabetes. However, only a third of cadaveric pancreas get to clinical transplantation due to low quality/number of islets. There is a need to identify biomarker(s) that predict the quality of islets, prior to initiating their isolation. Here, we sequenced transcriptome from 18 human islet preparations stratified into three groups (Gr.1: Best quality/transplantable islets, Gr.2: Intermediary quality, Gr.3: Inferior quality/non-transplantable islets) based on routine measurements including islet purity/viability. Machine-learning algorithms involving penalized regression analyses identified 10 long-non-coding(lnc)RNAs significantly different across all group-wise comparisons (Gr1VsGr2, Gr2vsGr3, Gr1vsGr3). Two variants of Metastasis-Associated Lung Adenocarcinoma Transcript-1(MALAT1) lncRNA were common across all comparisons. We confirmed RNA-seq findings in a "validation set" of 75 human islet preparations. Finally, in 19 pancreas samples, we demonstrate that assessing the levels of MALAT1 variants alone (ROC curve AUC: 0.83) offers highest specificity in predicting post-isolation islet quality and improves the predictive potential for clinical islet transplantation when combined with Edmonton Donor Points/Body Mass Index(BMI)/North American Islet Donor Score(NAIDS). We present this resource of islet-quality-stratified lncRNA transcriptome data and identify MALAT1 as a biomarker that significantly enhances current selection methods for clinical (GMP)-grade islet isolation.
OriginalsprogEngelsk
Artikelnummere129299
TidsskriftJCI Insight
Vol/bind4
Udgave nummer16
DOI
StatusUdgivet - 22 aug. 2019

Bibliografisk note

This article has been found as a ’Free Version’ from the Publisher on October 2 2019. When access to the article closes, please notify rucforsk@ruc.dk

Citer dette

Wong, W. W. K., Jiang, G., Sørensen, A. E., Chew, Y. V., Lee-Maynard, C., Liuwantara, D., Williams, L., O'Connell, P., Dalgaard, L. T., Ma, R. C., Hawthorne, W. J., Joglekar, M., & Hardikar, A. A. (2019). The long noncoding RNA MALAT1 predicts human pancreatic islet isolation quality. JCI Insight, 4(16), [e129299]. https://doi.org/10.1172/jci.insight.129299