miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions
Summary: Pluripotent stem cells hold great promise for regenerative medicine since they can differentiate into all somatic cells. MicroRNAs (miRNAs) could be important for the regulation of these cell-fate decisions. Profiling of miRNAs revealed 19 differentially expressed miRNAs in the endoderm and...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-11-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117304666 |
| _version_ | 1819086979943366656 |
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| author | Daichi Ishikawa Ulf Diekmann Jan Fiedler Annette Just Thomas Thum Sigurd Lenzen Ortwin Naujok |
| author_facet | Daichi Ishikawa Ulf Diekmann Jan Fiedler Annette Just Thomas Thum Sigurd Lenzen Ortwin Naujok |
| author_sort | Daichi Ishikawa |
| collection | DOAJ |
| description | Summary: Pluripotent stem cells hold great promise for regenerative medicine since they can differentiate into all somatic cells. MicroRNAs (miRNAs) could be important for the regulation of these cell-fate decisions. Profiling of miRNAs revealed 19 differentially expressed miRNAs in the endoderm and 29 in the mesoderm when analyzing FACS-purified cells derived from human embryonic stem cells. The mesodermal-enriched miR-483-3p was identified as an important regulator for the generation of mesodermal PDGFRA+ paraxial cells. Repression of its target PGAM1 significantly increased the number of PDGFRA+ cells. Furthermore, miR-483-3p, miR-199a-3p, and miR-214-3p might also have functions for the mesodermal progenitors. The endoderm-specific miR-489-3p and miR-1263 accelerated and increased endoderm differentiation upon overexpression. KLF4 was identified as a target of miR-1263. RNAi-mediated downregulation of KLF4 partially mimicked miR-1263 overexpression. Thus, the effects of this miRNA were mediated by facilitating differentiation through destabilization of pluripotency along with other not yet defined targets. : In this article, Ishikawa and colleagues show that miRNAs can regulate early cell-fate decisions during differentiation of human ESCs. miRNome profiling in pure endoderm and mesoderm revealed differentially expressed miRNAs. The endoderm-specific miR-489-3p and miR-1263 increased endoderm specification. The miR-1263 effect was mediated by KLF4 repression. The mesoderm-specific miR-483-3p regulated the generation PDGFRA+ paraxial cells via PGAM1 repression. Keywords: microRNA, miRNome, human pluripotent stem cell, endoderm, mesoderm, cell-fate decision, purified population |
| first_indexed | 2024-12-21T21:28:52Z |
| format | Article |
| id | doaj.art-4cde8c9a957f485293c727b9a81dc9f0 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-21T21:28:52Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-4cde8c9a957f485293c727b9a81dc9f02022-12-21T18:49:41ZengElsevierStem Cell Reports2213-67112017-11-019515881603miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate DecisionsDaichi Ishikawa0Ulf Diekmann1Jan Fiedler2Annette Just3Thomas Thum4Sigurd Lenzen5Ortwin Naujok6Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; Department of Surgery, Tokushima University, 3-18-15, Kuramoto, Tokushima 770-8503, JapanInstitute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; National Heart and Lung Institute, Imperial College London, Sydney Street, London SW3 6NP, UKInstitute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, GermanyInstitute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany; Corresponding authorSummary: Pluripotent stem cells hold great promise for regenerative medicine since they can differentiate into all somatic cells. MicroRNAs (miRNAs) could be important for the regulation of these cell-fate decisions. Profiling of miRNAs revealed 19 differentially expressed miRNAs in the endoderm and 29 in the mesoderm when analyzing FACS-purified cells derived from human embryonic stem cells. The mesodermal-enriched miR-483-3p was identified as an important regulator for the generation of mesodermal PDGFRA+ paraxial cells. Repression of its target PGAM1 significantly increased the number of PDGFRA+ cells. Furthermore, miR-483-3p, miR-199a-3p, and miR-214-3p might also have functions for the mesodermal progenitors. The endoderm-specific miR-489-3p and miR-1263 accelerated and increased endoderm differentiation upon overexpression. KLF4 was identified as a target of miR-1263. RNAi-mediated downregulation of KLF4 partially mimicked miR-1263 overexpression. Thus, the effects of this miRNA were mediated by facilitating differentiation through destabilization of pluripotency along with other not yet defined targets. : In this article, Ishikawa and colleagues show that miRNAs can regulate early cell-fate decisions during differentiation of human ESCs. miRNome profiling in pure endoderm and mesoderm revealed differentially expressed miRNAs. The endoderm-specific miR-489-3p and miR-1263 increased endoderm specification. The miR-1263 effect was mediated by KLF4 repression. The mesoderm-specific miR-483-3p regulated the generation PDGFRA+ paraxial cells via PGAM1 repression. Keywords: microRNA, miRNome, human pluripotent stem cell, endoderm, mesoderm, cell-fate decision, purified populationhttp://www.sciencedirect.com/science/article/pii/S2213671117304666 |
| spellingShingle | Daichi Ishikawa Ulf Diekmann Jan Fiedler Annette Just Thomas Thum Sigurd Lenzen Ortwin Naujok miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions Stem Cell Reports |
| title | miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions |
| title_full | miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions |
| title_fullStr | miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions |
| title_full_unstemmed | miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions |
| title_short | miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions |
| title_sort | mirnome profiling of purified endoderm and mesoderm differentiated from hescs reveals functions of mir 483 3p and mir 1263 for cell fate decisions |
| url | http://www.sciencedirect.com/science/article/pii/S2213671117304666 |
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