Clinical findings and data obtained in animal models indicate that nutrient uptake and exposure to environmental agents during pregnancy may affect fetal/newborn gestational programming, thereby resulting in obesity and/or obesity-related disorders in offspring. Human amniotic mesenchymal stem cells (hA-MSCs) differentiate into adipocytes and are thus a suitable model to investigate adipocyte functions in obesity. The aim of this study was to elucidate the miRNome of hA-MSCs and its contribution to obesity in pregnancy. To this aim we used the following: (i) high-resolution small RNA sequencing to characterize the microRNA (miRNA) profiles of hA-MSCs of 13 obese (Ob-) and 7 control (Co-) pregnant women at delivery; (ii) multiple-method integrated bioinformatics to predict the metabolic pathways potentially miRNA deregulated in Ob-hA-MSCs; and (iii) microarray mRNA expression profiling to verify obese-associated mRNA alterations. In summary, 12 miRNAs were differentially expressed between Ob-hA-MSCs and Co-hA-MSCs, with a multiple-methods bioinformatic consensus on miR-138-5p and miR-222-3p, which were overexpressed in Ob-hA-MSCs versus Co-hA-MSCs. The top 20 significant pathways predicted to be deregulated through miR-138-5p and/or miR-222-3p/target interaction included fat cell differentiation and deposits, lipid/carbohydrate homeostasis, response to stress, metabolic syndrome, heart disease, and ischemia. In conclusion, our finding of miR-138-5p/miR-222-3p overexpression in Ob-hA-MSCs, together with the transcriptomic data, suggests that these miRNAs in obese pregnancy could derange metabolic pathways previously found impaired in tissues from obese adults or in obesity-associated disorders and concur to modify gestational programming as has been demonstrated in animal models. This raises the possibility of using diet-based strategies to normalize the perinatal miRNome in obesity.

miR-138/miR-222 Overexpression Characterizes the miRNome of Amniotic Mesenchymal Stem Cells in Obesity / Nardelli, C; Granata, I; Iaffaldano, L; D'Argenio, V; Del Monaco, V; Maruotti, Gm; Omodei, D; Del Vecchio, L; Martinelli, P; Salvatore, F; Guarracino, M R; Sacchetti, L; Pastore, L. - In: STEM CELLS AND DEVELOPMENT. - ISSN 1547-3287. - 26:1(2017), pp. 4-14. [10.1089/scd.2016.0127]

miR-138/miR-222 Overexpression Characterizes the miRNome of Amniotic Mesenchymal Stem Cells in Obesity

Nardelli C;Iaffaldano L;D'Argenio V;Del Monaco V;Maruotti GM;Omodei D;Sacchetti L;Pastore L
2017

Abstract

Clinical findings and data obtained in animal models indicate that nutrient uptake and exposure to environmental agents during pregnancy may affect fetal/newborn gestational programming, thereby resulting in obesity and/or obesity-related disorders in offspring. Human amniotic mesenchymal stem cells (hA-MSCs) differentiate into adipocytes and are thus a suitable model to investigate adipocyte functions in obesity. The aim of this study was to elucidate the miRNome of hA-MSCs and its contribution to obesity in pregnancy. To this aim we used the following: (i) high-resolution small RNA sequencing to characterize the microRNA (miRNA) profiles of hA-MSCs of 13 obese (Ob-) and 7 control (Co-) pregnant women at delivery; (ii) multiple-method integrated bioinformatics to predict the metabolic pathways potentially miRNA deregulated in Ob-hA-MSCs; and (iii) microarray mRNA expression profiling to verify obese-associated mRNA alterations. In summary, 12 miRNAs were differentially expressed between Ob-hA-MSCs and Co-hA-MSCs, with a multiple-methods bioinformatic consensus on miR-138-5p and miR-222-3p, which were overexpressed in Ob-hA-MSCs versus Co-hA-MSCs. The top 20 significant pathways predicted to be deregulated through miR-138-5p and/or miR-222-3p/target interaction included fat cell differentiation and deposits, lipid/carbohydrate homeostasis, response to stress, metabolic syndrome, heart disease, and ischemia. In conclusion, our finding of miR-138-5p/miR-222-3p overexpression in Ob-hA-MSCs, together with the transcriptomic data, suggests that these miRNAs in obese pregnancy could derange metabolic pathways previously found impaired in tissues from obese adults or in obesity-associated disorders and concur to modify gestational programming as has been demonstrated in animal models. This raises the possibility of using diet-based strategies to normalize the perinatal miRNome in obesity.
2017
miR-138/miR-222 Overexpression Characterizes the miRNome of Amniotic Mesenchymal Stem Cells in Obesity / Nardelli, C; Granata, I; Iaffaldano, L; D'Argenio, V; Del Monaco, V; Maruotti, Gm; Omodei, D; Del Vecchio, L; Martinelli, P; Salvatore, F; Guarracino, M R; Sacchetti, L; Pastore, L. - In: STEM CELLS AND DEVELOPMENT. - ISSN 1547-3287. - 26:1(2017), pp. 4-14. [10.1089/scd.2016.0127]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/660487
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