Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification

Abstract MicroRNAs (miRNAs) are known to be crucial players in governing the differentiation of human induced pluripotent stem cells (hiPSCs). Despite their utter importance, identifying key lineage specifiers among the myriads of expressed miRNAs remains challenging. We believe that the current pra...

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Autores principales:	Lu Li, Kai-Kei Miu, Shen Gu, Hoi-Hung Cheung, Wai-Yee Chan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d475e2fe14ca483e9ce005b1662ce96f
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spelling	oai:doaj.org-article:d475e2fe14ca483e9ce005b1662ce96f2021-12-02T15:08:13ZComparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification10.1038/s41598-018-27719-02045-2322https://doaj.org/article/d475e2fe14ca483e9ce005b1662ce96f2018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27719-0https://doaj.org/toc/2045-2322Abstract MicroRNAs (miRNAs) are known to be crucial players in governing the differentiation of human induced pluripotent stem cells (hiPSCs). Despite their utter importance, identifying key lineage specifiers among the myriads of expressed miRNAs remains challenging. We believe that the current practice in mining miRNA specifiers via delineating dynamic fold-changes only is inadequate. Our study, therefore, provides evidence to pronounce “lineage specificity” as another important attribute to qualify for these lineage specifiers. Adopted hiPSCs were differentiated into representative lineages (hepatic, nephric and neuronal) over all three germ layers whilst the depicted miRNA expression changes compiled into an integrated atlas. We demonstrated inter-lineage analysis shall aid in the identification of key miRNAs with lineage-specificity, while these shortlisted candidates were collectively known as “lineage-specific miRNAs”. Subsequently, we followed through the fold-changes along differentiation via computational analysis to identify miR-192 and miR-372-3p, respectively, as representative candidate key miRNAs for the hepatic and nephric lineages. Indeed, functional characterization validated that miR-192 and miR-372-3p regulate lineage differentiation via modulation of the expressions of lineage-specific genes. In summary, our presented miRNA atlas is a resourceful ore for the mining of key miRNAs responsible for lineage specification.Lu LiKai-Kei MiuShen GuHoi-Hung CheungWai-Yee ChanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lu Li Kai-Kei Miu Shen Gu Hoi-Hung Cheung Wai-Yee Chan Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification
description	Abstract MicroRNAs (miRNAs) are known to be crucial players in governing the differentiation of human induced pluripotent stem cells (hiPSCs). Despite their utter importance, identifying key lineage specifiers among the myriads of expressed miRNAs remains challenging. We believe that the current practice in mining miRNA specifiers via delineating dynamic fold-changes only is inadequate. Our study, therefore, provides evidence to pronounce “lineage specificity” as another important attribute to qualify for these lineage specifiers. Adopted hiPSCs were differentiated into representative lineages (hepatic, nephric and neuronal) over all three germ layers whilst the depicted miRNA expression changes compiled into an integrated atlas. We demonstrated inter-lineage analysis shall aid in the identification of key miRNAs with lineage-specificity, while these shortlisted candidates were collectively known as “lineage-specific miRNAs”. Subsequently, we followed through the fold-changes along differentiation via computational analysis to identify miR-192 and miR-372-3p, respectively, as representative candidate key miRNAs for the hepatic and nephric lineages. Indeed, functional characterization validated that miR-192 and miR-372-3p regulate lineage differentiation via modulation of the expressions of lineage-specific genes. In summary, our presented miRNA atlas is a resourceful ore for the mining of key miRNAs responsible for lineage specification.
format	article
author	Lu Li Kai-Kei Miu Shen Gu Hoi-Hung Cheung Wai-Yee Chan
author_facet	Lu Li Kai-Kei Miu Shen Gu Hoi-Hung Cheung Wai-Yee Chan
author_sort	Lu Li
title	Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification
title_short	Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification
title_full	Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification
title_fullStr	Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification
title_full_unstemmed	Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification
title_sort	comparison of multi-lineage differentiation of hipscs reveals novel mirnas that regulate lineage specification
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d475e2fe14ca483e9ce005b1662ce96f
work_keys_str_mv	AT luli comparisonofmultilineagedifferentiationofhipscsrevealsnovelmirnasthatregulatelineagespecification AT kaikeimiu comparisonofmultilineagedifferentiationofhipscsrevealsnovelmirnasthatregulatelineagespecification AT shengu comparisonofmultilineagedifferentiationofhipscsrevealsnovelmirnasthatregulatelineagespecification AT hoihungcheung comparisonofmultilineagedifferentiationofhipscsrevealsnovelmirnasthatregulatelineagespecification AT waiyeechan comparisonofmultilineagedifferentiationofhipscsrevealsnovelmirnasthatregulatelineagespecification
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Comparison of multi-lineage differentiation of hiPSCs reveals novel miRNAs that regulate lineage specification

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