Epigenetic regulation of amniotic fluid mesenchymal stem cell differentiation to the mesodermal lineages at normal and fetus‐diseased gestation

Human mesenchymal stem cells isolated from amniotic fluid (AF‐MSCs) demonstrate the potency for self‐renewal and multidifferentiation, and can, therefore, be a potential alternative source of stem cells adapted for therapeutic purposes. The object of this study is to evaluate the efficacy of MSCs fr...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2020-02, Vol.121 (2), p.1811-1822
Main Authors: Zentelytė, Aistė, Gasiūnienė, Monika, Treigytė, Gražina, Baronaitė, Sandra, Savickienė, Jūratė, Borutinskaitė, Veronika, Navakauskienė, Rūta
Format: Article
Language:English
Subjects:
Adipocytes
Adipocytes - cytology
Adipocytes - metabolism
Adiponectin
Alkaline phosphatase
Amniotic fluid
Amniotic Fluid - cytology
Amniotic Fluid - metabolism
amniotic fluid stem cells
Autografts
Biomarkers
Biomedical materials
CD105 antigen
CD44 antigen
CD90 antigen
Cell Differentiation
Cell Lineage
Cell morphology
Cell self-renewal
Cell surface
Cytology
differentiation
Differentiation (biology)
DNMT1 protein
Epigenetics
Fetal Diseases - genetics
Fetal Diseases - metabolism
Fetal Diseases - pathology
Fetus - cytology
Fetus - metabolism
Fetuses
Gene expression
Gene Expression Regulation, Developmental
Genes
Gestation
Gestational Age
histone modifications
Humans
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Mesenchyme
Mesoderm - cytology
Mesoderm - metabolism
miRNA
Morphology
Oct-4 protein
Osteoblastogenesis
Osteoblasts
Osteoblasts - cytology
Osteoblasts - metabolism
Osteocalcin
Osteopontin
Pregnancy
Stem cells
Therapeutic applications
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Summary:Human mesenchymal stem cells isolated from amniotic fluid (AF‐MSCs) demonstrate the potency for self‐renewal and multidifferentiation, and can, therefore, be a potential alternative source of stem cells adapted for therapeutic purposes. The object of this study is to evaluate the efficacy of MSCs from AF when the pregnancy is normal or when the fetus is affected during pregnancy to differentiate into mesodermal lineage tissues and to elucidate epigenetic states responsible for terminal adipogenic and osteogenic differentiation. The morphology of AF‐MSCs from two cell sources and the expression of the cell surface‐specific (CD44, CD90, and CD105) markers and pluripotency (Oct4, Nanog, Sox2, and Rex1) genes were quite similar and underwent mesodermal lineage differentiation because this is shown by the typical cell morphology and of genes’ expression specific for adipogenic (peroxisome proliferator‐activated receptor‐ɣ, adiponectin) and osteoblastic (alkaline phosphatase, osteopontin, and osteocalcin) differentiation. Terminal lineage‐specific differentiation was related to differential expression of miR‐17, miR‐21, miR‐34a, and miR‐146a, decreased levels of acetylated H4 and H3K9, trimethylated H3K4 and H3K9, and the retention of H3K27me3 along with a reduction in the levels of HDAC1, DNMT1, and PRC1/2 proteins (BMI1/SUZ12). No significant distinction could be identified in the levels of expression of all epigenetic or pluripotency markers between undifferentiated MSCs isolated from AF of normal gestation and pregnancy where the fetus was damaged and between those differentiated toward adipocytes or osteoblasts. The expressional changes of those marks and microRNAs that occurred during terminal differentiation to mesodermal tissues indicate subtle epigenetic regulation in AF‐MSCs when the condition of the fetus is healthy normal or diseased. More detailed studies of epigenetic mechanisms may offer a better understanding of AF‐MSCs differentiation in fetus‐diseased conditions and their usage in an autologous therapeutic application and prenatal disease research. Amniotic fluid‐derived mesenchymal stem cells (AF‐MSCs) from healthy pregnancies and fetus‐diseased gestations represent a population of stem cells, the origin of which is mesenchymal and which have quite similar expression profile of cell surface and pluripotency markers and shear the similar differentiation potential through rather similar epigenetic mechanisms regulating chromatin modifications du
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.29416