The long noncoding RNA MALAT1 predicts human islet isolation quality

Wong, Wilson; Jiang, Guochi; Sørensen, Anja Elaine; Chew, Yi Vee; Lee-Maynard, Cody; Liuwantara, David; Williams, Lindy; OʼConnell, P J.; Dalgaard, Louise Torp; Ronald, C.; Hawthorne, Wayne J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.

doi:10.1172/jci.insight.129299

Cited by 18 publications

(14 citation statements)

References 53 publications

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“…Many of the molecular mechanisms that underlie the formation of pancreatic endocrine cells have been defined ( Romer and Sussel, 2015 ; Schiesser and Wells, 2014 ). However, despite some evidence that long noncoding RNAs (lncRNAs) are important for proper development and function of pancreatic beta cells ( Arnes et al, 2016 ; Morán et al, 2012 ; Wong et al, 2019 ), a systematic functional assessment of the noncoding transcriptome during pancreas development is lacking.…”

Section: Introductionmentioning

confidence: 99%

A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

Gaertner

Heesch

Schneider-Lunitz

et al. 2020

eLife

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Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion of LINC00261 diminishes insulin+ cells, in a manner independent of the nearby TF FOXA2. One-by-one deletion of each of LINC00261's open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic differentiation and provides a blueprint for dissection of their coding and noncoding roles.

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Section: Introductionmentioning

confidence: 99%

A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

Gaertner

Heesch

Schneider-Lunitz

et al. 2020

eLife

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“…Here, microRNAs are ranked based on the level of significant change (p value) that each of the microRNAs induced to either increase (shown in green) or decrease (shown in red) target mRNA gene expression. As an alternate validation, we assessed the expression levels of these microRNAs and islet mRNAs in our bulk RNA-seq data sets ( GSE134068 ; n = 18 ( Wong et al., 2019 )) and correlated selected microRNAs (miR-375, miR-141, miR-30d, and miR-216b) with key pancreatic gene transcripts. As shown in ( Figure 4 B), several pancreatic genes positively correlated with miR-375, while negatively correlating with the levels of miR-216b (or miR-30d) in human islets.…”

Section: Resultsmentioning

confidence: 99%

Machine learning workflows identify a microRNA signature of insulin transcription in human tissues

Wong

Joglekar²,

Saini³

et al. 2021

iScience

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“…It seemed that transplantation of MALAT1-MSCs has some effects on beta-cells in STZ-treated mice, although the effects may be delicate and did not reach significance in the measurement of beta-cell mass. Interestingly, it has been reported that MALAT1 is highly expressed in the pancreas [19]. Thus, MALAT1 may play critical roles in beta-cell homeostasis and function.…”

Section: Discussionmentioning

confidence: 99%

Improved therapeutic effects on diabetic foot by human mesenchymal stem cells expressing MALAT1 as a sponge for microRNA-205-5p

Zhu

Zhong

Yang

et al. 2019

Aging

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Diabetic foot (DF) is a common complication of high severity for diabetes, a prevalent metabolic disorder that affects billions of people worldwide. Mesenchymal stem cells (MSCs) have a demonstrative therapeutic effect on DF, through their generation of pro-angiogenesis factors, like vascular endothelial growth factor (VEGF). Recently, genetically modified MSCs have been used in therapy and we have shown that depletion of micoRNA-205-5p (miR-205-5p) in human MSCs promotes VEGF-mediated therapeutic effects on DF. Here, we showed that a long non-coding RNA (lncRNA), MALAT1, is a competing endogenous RNA (ceRNA) for miR-205-5p, and is low expressed in human MSCs. Ectopic expression of MALAT1 in human MSCs significantly decreased miR-205-5p levels, resulting in upregulation of VEGF production and improved in vitro endothelial cell tube formation. In a DF model in immunodeficient NOD/SCID mice, transplantation of human miR-205-5p-depleted MSCs exhibited better therapeutic effects on DF recovery than control MSCs. Moreover, MALAT1-expressing MSCs showed even better therapeutic effects on DF recovery than miR-205-5p-depleted MSCs. This difference in DF recovery was shown to be associated with the levels of on-site vascularization. Together, our data suggest that MALAT1 functions as a sponge RNA for miR-205-5p to increase therapeutic effects of MSCs on DF.

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The long noncoding RNA MALAT1 predicts human islet isolation quality

Cited by 18 publications

References 53 publications

A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

Machine learning workflows identify a microRNA signature of insulin transcription in human tissues

Improved therapeutic effects on diabetic foot by human mesenchymal stem cells expressing MALAT1 as a sponge for microRNA-205-5p

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