학술논문

miRNAs as cell fate determinants of lateral and paraxial mesoderm differentiation from embryonic stem cells.
Document Type
Article
Source
Developmental Biology. Oct2021, Vol. 478, p212-221. 10p.
Subject
*EMBRYONIC stem cells
*MESODERM
*MICRORNA
*MYOBLASTS
*SKELETAL muscle
Language
ISSN
0012-1606
Abstract
To date, the role of miRNAs on pluripotency and differentiation of ESCs into specific lineages has been studied extensively. However, the specific role of miRNAs during lateral and paraxial mesoderm cell fate decision is still unclear. To address this, we firstly determined miRNA profile of mouse ESCs differentiating towards lateral and paraxial lineages which were detected using Flk1 and PDGFαR antibodies, and of myogenic and hematopoietic differentiation potential of purified paraxial and lateral mesodermal cells within these populations. miRNAs associated with lateral and paraxial mesoderm, and their targets were identified using bioinformatics tools. The targets of the corresponding miRNAs were validated after transfection into mouse ESCs. The roles of the selected miRNAs in lateral, and paraxial mesoderm formation were assessed along with hematopoietic and myogenic differentiation capacity. Among the miRNAs, mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p, upregulated in lateral mesoderm cells, and mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p, upregulated in paraxial mesoderm cells. While transient co-transfection of mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p increased the number of lateral mesodermal cells, co-transfection of mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p increased the number of paraxial mesodermal cells. Moreover, differentiation potential of the lateral mesodermal cells into hematopoietic cell lineage increased upon co-transfection of mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p and differentiation potential of the paraxial mesodermal cells into skeletal muscle lineage were increased upon co-transfection of mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p. In conclusion, we determined the miRNA profile of lateral and paraxial mesodermal cells and co-transfection of miRNAs increased differentiation potential of both lateral and paraxial mesodermal cells transiently. [Display omitted] • miRNA profile of Flk1+PDGFαR− and Flk1−PDGFαR+ were determined for the first time. • mmu-miR-126a-3p, mmu-miR-335-5p and mmu-672-5p were upregulated in lateral mesodermal cells. • mmu-10b-5p, mmu-196a-5p and mmu-miR-615-3p were upregulated in paraxial mesodermal cells. • miRNAs can facilitate both lateral and paraxial mesoderm differentiation. • miRNAs can also induce differentiation potential of lateral and paraxial mesoderm cells. [ABSTRACT FROM AUTHOR]