Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency

Summary: Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provi...

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Main Authors: Sharif Moradi, Ali Sharifi-Zarchi, Amirhossein Ahmadi, Sepideh Mollamohammadi, Alexander Stubenvoll, Stefan Günther, Ghasem Hosseini Salekdeh, Sassan Asgari, Thomas Braun, Hossein Baharvand
Format: Article
Language:English
Published: Elsevier 2017-12-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117304642
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author Sharif Moradi
Ali Sharifi-Zarchi
Amirhossein Ahmadi
Sepideh Mollamohammadi
Alexander Stubenvoll
Stefan Günther
Ghasem Hosseini Salekdeh
Sassan Asgari
Thomas Braun
Hossein Baharvand
author_facet Sharif Moradi
Ali Sharifi-Zarchi
Amirhossein Ahmadi
Sepideh Mollamohammadi
Alexander Stubenvoll
Stefan Günther
Ghasem Hosseini Salekdeh
Sassan Asgari
Thomas Braun
Hossein Baharvand
author_sort Sharif Moradi
collection DOAJ
description Summary: Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the âmiRNomeâ of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most âground-state miRNAsâ are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the Dlk1-Dio3 locus (miR-541-5p, miR-410-3p, and miR-381-3p) promoted pluripotency via inhibition of multi-lineage differentiation and stimulation of self-renewal. Overall, our results demonstrate that ground-state pluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation. : Ground-state pluripotency is a cell state in which pluripotency is maintained through inhibition of differentiation. In this paper, Baharvand and colleagues report that ground-state pluripotency is associated with a unique microRNA signature. They find that ground-state microRNAs, which are mostly encoded by the Dlk1-Dio3 locus, contribute to the maintenance of ESCs through stimulating self-renewal and inhibiting differentiation. Keywords: Dlk1-Dio3 locus, ground-state pluripotency, microRNA, small RNA sequencing, differentiation, self-renewal, Sfmbt2 locus
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spelling doaj.art-4c0ae320b5cb43b08d78f9e9568b1f722022-12-21T23:51:53ZengElsevierStem Cell Reports2213-67112017-12-019620812096Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State PluripotencySharif Moradi0Ali Sharifi-Zarchi1Amirhossein Ahmadi2Sepideh Mollamohammadi3Alexander Stubenvoll4Stefan Günther5Ghasem Hosseini Salekdeh6Sassan Asgari7Thomas Braun8Hossein Baharvand9Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, Iran; Computer Engineering Department, Sharif University of Technology, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, IranMax-Planck Institute for Heart and Lung Research, Department of Cardiac Development and Remodelling, Ludwigstrasse 43, 61231 Bad Nauheim, GermanyMax-Planck Institute for Heart and Lung Research, Department of Cardiac Development and Remodelling, Ludwigstrasse 43, 61231 Bad Nauheim, GermanyDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, IranAustralian Infectious Disease Research Centre, School of Biological Sciences, The University of Queensland, Brisbane, QLD, AustraliaMax-Planck Institute for Heart and Lung Research, Department of Cardiac Development and Remodelling, Ludwigstrasse 43, 61231 Bad Nauheim, Germany; Corresponding authorDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran; Corresponding authorSummary: Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the âmiRNomeâ of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most âground-state miRNAsâ are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the Dlk1-Dio3 locus (miR-541-5p, miR-410-3p, and miR-381-3p) promoted pluripotency via inhibition of multi-lineage differentiation and stimulation of self-renewal. Overall, our results demonstrate that ground-state pluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation. : Ground-state pluripotency is a cell state in which pluripotency is maintained through inhibition of differentiation. In this paper, Baharvand and colleagues report that ground-state pluripotency is associated with a unique microRNA signature. They find that ground-state microRNAs, which are mostly encoded by the Dlk1-Dio3 locus, contribute to the maintenance of ESCs through stimulating self-renewal and inhibiting differentiation. Keywords: Dlk1-Dio3 locus, ground-state pluripotency, microRNA, small RNA sequencing, differentiation, self-renewal, Sfmbt2 locushttp://www.sciencedirect.com/science/article/pii/S2213671117304642
spellingShingle Sharif Moradi
Ali Sharifi-Zarchi
Amirhossein Ahmadi
Sepideh Mollamohammadi
Alexander Stubenvoll
Stefan Günther
Ghasem Hosseini Salekdeh
Sassan Asgari
Thomas Braun
Hossein Baharvand
Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
Stem Cell Reports
title Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
title_full Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
title_fullStr Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
title_full_unstemmed Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
title_short Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency
title_sort small rna sequencing reveals dlk1 dio3 locus embedded micrornas as major drivers of ground state pluripotency
url http://www.sciencedirect.com/science/article/pii/S2213671117304642
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