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A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells

Human pluripotent stem cells (hPSCs) represent a promising platform for studying embryonic development, and different states of pluripotency reflect the different stages of embryo development. Here, we successfully converted three in-house-derived primed hPSC lines (H10, H24, and iPS) to a naive sta...

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Autores principales: Ma, Zhenglai, Li, Yanni, Zhang, Yingying, Chen, Jiaxin, Tan, Tao, Fan, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297305/
https://www.ncbi.nlm.nih.gov/pubmed/32544168
http://dx.doi.org/10.1371/journal.pone.0234628
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author Ma, Zhenglai
Li, Yanni
Zhang, Yingying
Chen, Jiaxin
Tan, Tao
Fan, Yong
author_facet Ma, Zhenglai
Li, Yanni
Zhang, Yingying
Chen, Jiaxin
Tan, Tao
Fan, Yong
author_sort Ma, Zhenglai
collection PubMed
description Human pluripotent stem cells (hPSCs) represent a promising platform for studying embryonic development, and different states of pluripotency reflect the different stages of embryo development. Here, we successfully converted three in-house-derived primed hPSC lines (H10, H24, and iPS) to a naive state and an expanded pluripotent stem cell (EPS) state. Primed, naive and EPS cells displayed state-specific morphologies and expressed pluripotent markers. The expression of SSEA4 and TRA-1-60 was downregulated in the conversion process. The H3K27me3 expression level also decreased, indicating that global methylation was reduced and that the X chromosome started to reactivate. RNA-sequencing analysis results revealed that differentially expressed genes (DEGs) were significantly enriched in both naive hPSCs and EPS cells when compared to the primed state. However, imprinted gene expression barely changed before and after state reversion. Gene ontology (GO) analyses showed that the upregulated DEGs were mostly enriched in RNA processing, DNA replication and repair, and regulation of cell cycle process, while downregulated DEGs were related to extracellular adhesion and various tissue developmental processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that EPS cells were enriched in the PI3K-Akt and Wnt signaling pathways. Analysis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network between primed, naive hPSCs and EPS cells revealed that hsa-miR-424-5p, has-miR-16-5p, has-miR-27b-3p, has-miR-29c-3p, and KCNQ1OT1 were crucial nodes with high degrees of connectivity. Our work may represent new insight into the intrinsic molecular features of different hPSC states.
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spelling pubmed-72973052020-06-19 A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells Ma, Zhenglai Li, Yanni Zhang, Yingying Chen, Jiaxin Tan, Tao Fan, Yong PLoS One Research Article Human pluripotent stem cells (hPSCs) represent a promising platform for studying embryonic development, and different states of pluripotency reflect the different stages of embryo development. Here, we successfully converted three in-house-derived primed hPSC lines (H10, H24, and iPS) to a naive state and an expanded pluripotent stem cell (EPS) state. Primed, naive and EPS cells displayed state-specific morphologies and expressed pluripotent markers. The expression of SSEA4 and TRA-1-60 was downregulated in the conversion process. The H3K27me3 expression level also decreased, indicating that global methylation was reduced and that the X chromosome started to reactivate. RNA-sequencing analysis results revealed that differentially expressed genes (DEGs) were significantly enriched in both naive hPSCs and EPS cells when compared to the primed state. However, imprinted gene expression barely changed before and after state reversion. Gene ontology (GO) analyses showed that the upregulated DEGs were mostly enriched in RNA processing, DNA replication and repair, and regulation of cell cycle process, while downregulated DEGs were related to extracellular adhesion and various tissue developmental processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that EPS cells were enriched in the PI3K-Akt and Wnt signaling pathways. Analysis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network between primed, naive hPSCs and EPS cells revealed that hsa-miR-424-5p, has-miR-16-5p, has-miR-27b-3p, has-miR-29c-3p, and KCNQ1OT1 were crucial nodes with high degrees of connectivity. Our work may represent new insight into the intrinsic molecular features of different hPSC states. Public Library of Science 2020-06-16 /pmc/articles/PMC7297305/ /pubmed/32544168 http://dx.doi.org/10.1371/journal.pone.0234628 Text en © 2020 Ma et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ma, Zhenglai
Li, Yanni
Zhang, Yingying
Chen, Jiaxin
Tan, Tao
Fan, Yong
A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells
title A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells
title_full A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells
title_fullStr A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells
title_full_unstemmed A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells
title_short A lncRNA-miRNA-mRNA network for human primed, naive and extended pluripotent stem cells
title_sort lncrna-mirna-mrna network for human primed, naive and extended pluripotent stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297305/
https://www.ncbi.nlm.nih.gov/pubmed/32544168
http://dx.doi.org/10.1371/journal.pone.0234628
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