Integrated Transcriptome Analysis of microRNA and mRNA in Mouse Skin Derived Precursors (SKPs) and SKP Derived Fibroblast (SFBs) by RNA-Seq

Author(s): Rongying Zhou, Yujie Mao, Lidan Xiong, Li Li*.

Journal Name: Current Genomics

Volume 20 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Skin-derived precursors (SKPs) display the characteristics of self-renewal and multilineage differentiation.

Objective: The study aimed to explore the molecular mechanisms of mouse SKPs differentiation into SKP-derived fibroblasts (SFBs).

Methods: We compared the microRNA (miRNA) profile in mouse SKPs and SFBs by RNA sequencing. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to validate the miRNA expression. The integrated analysis of miRNA and mRNA expression data was performed to explore the potential crosstalk of miRNA-mRNA in SKP differentiation.

Results: 207 differentially expressed miRNAs and 835 miRNA target genes in the gene list of integrated mRNA expression profiling were identified. Gene Ontology (GO) enrichment analysis revealed that cell differentiation and cell proliferation process were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the target genes were significantly most enriched in the cytokine-cytokine receptor interaction, cancer pathways and axon guidance signaling pathway. The most upregulated and downregulated target genes were involved in the Wnt, Notch, cytokine- cytokine receptor interaction, TGF-β, p53 and apoptotic signaling pathway. The miRNAmRNA regulatory networks and 507 miRNA-mRNA pairs were constructed. Seven miRNAs (miR- 486-3p, miR-504-5p, miR-149-3p, miR-31-5p, miR-484, miR-328-5p and miR-22-5p) and their target genes Wnt4, Dlx2, Sema4f, Kit, Kitl, Inpp5d, Igfbp3, Prdm16, Sfn, Irf6 and Clu were identified as miRNA-mRNA crosstalk pairs.

Conclusion: These genes and signaling pathways might control SKPs proliferation and SKPs differentiation into SFBs during the process of SKPs differentiation, which might promote the application of SKPs in the clinical treatment of skin-related diseases by regulating SKPs proliferation and SKPs differentiation.

Keywords: Skin derived precursors, Fibroblasts, Stem cell, RNA sequencing, Transcriptome analysis, microRNA.

Toma, J.G.; Akhavan, M.; Fernandes, K.J.; Barnabé-Heider, F.; Sadikot, A.; Kaplan, D.R.; Miller, F.D. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol., 2001, 3(9), 778-784.
Dyce, P.W.; Zhu, H.; Craig, J.; Li, J. Stem cells with multilineage potential derived from porcine skin. Biochem. Biophys. Res. Commun., 2004, 316(3), 651-658.
Fernandes, K.J.; McKenzie, I.A.; Mill, P.; Smith, K.M.; Akhavan, M.; Barnabé-Heider, F.; Biernaskie, J.; Junek, A.; Kobayashi, N.R.; Toma, J.G.; Kaplan, D.R.; Labosky, P.A.; Rafuse, V.; Hui, C.C.; Miller, F.D. A dermal niche for multipotent adult skin-derived precursor cells. Nat. Cell Biol., 2004, 6(11), 1082-1093.
Kang, H.K.; Min, S.K.; Jung, S.Y.; Jung, K.; Jang, D.H.; Kim, O.B.; Chun, G.S.; Lee, Z.H.; Min, B.M. The potential of mouse skin-derived precursors to differentiate into mesenchymal and neural lineages and their application to osteogenic induction in vivo. Int. J. Mol. Med., 2011, 28(6), 1001-1011.
Mandai, M.; Kurimoto, Y.; Takahashi, M. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med., 2017, 377(8), 792-793.
Biernaskie, J.; Miller, F. Skin-derived precursors (SKPs): In vivo cell fate is limited to the neural crest lineage, and is determined by tissue-specific factors. Int. J. Dev. Neurosci., 2006, 24(8), 514.
Zhao, M.T.; Whitworth, K.M.; Zhang, X.; Zhao, J.; Miao, Y.L.; Zhang, Y.; Prather, R.S. Deciphering the mesodermal potency of porcine skin-derived progenitors (SKP) by microarray analysis. Reprogram., 2010, 12(2), 161-173.
Zhong, J.; Li, L. Skin-derived precursors against UVB-induced apoptosis via Bcl-2 and Nrf2 upregulation. BioMed Res. Int., 2016, 2016(1), 6894743.
Mao, Y.; Xiong, L.; Wang, S.; Zhong, J.; Zhou, R.; Li, L. Comparison of the transcriptomes of mouse skin derived precursors (SKPs) and SKP-derived fibroblasts (SFBs) by RNA-Seq. PLoS One, 2015, 10(2), e0117739.
Li, R.; Yu, C.; Li, Y.; Lam, T.W.; Yiu, S.M.; Kristiansen, K.; Wang, J. SOAP2: An improved ultrafast tool for short read alignment. Bioinformatics, 2009, 25(15), 1966-1967.
Jiang, M.; Sun, Z.; Dang, E.; Li, B.; Fang, H.; Li, J.; Gao, L.; Zhang, K.; Wang, G. TGFβ/SMAD/microRNA-486-3p signaling axis mediates keratin 17 expression and keratinocyte hyperproliferation in psoriasis. J. Invest. Dermatol., 2017, 137(10), 2177-2186.
Ye, H.; Yu, X.; Xia, J.; Tang, X.; Tang, L.; Chen, F. MiR-486-3p targeting ECM1 represses cell proliferation and metastasis in cervical cancer. Biomed. Pharmacother., 2016, 80, 109-114.
Tayyeb, A.; Shahzad, N.; Ali, G. Differentiation of mesenchymal stem cells towards nephrogenic lineage and their enhanced resistance to oxygen peroxide-induced oxidative stress. Iran. J. Kidney Dis., 2017, 11(4), 271-279.
Liu, R.; Li, N.; Lin, Y.; Wang, M.; Peng, Y.; Lewi, K.; Wang, Q. Glucagon like peptide-1 promotes adipocyte differentiation via the Wnt4 mediated sequestering of beta-catenin. PLoS One, 2016, 11(8), e0160212.
Zhang, Q.; Zagozewski, J.; Cheng, S.; Dixit, R.; Zhang, S.; de Melo, J.; Mu, X.; Klein, W.H.; Brown, N.L.; Wigle, J.T.; Schuurmans, C.; Eisenstat, D.D. Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina. Development, 2017, 144(9), 1698-1711.
Sun, H.; Liu, Z.; Li, B.; Dai, J.; Wang, X. Effects of DLX2 overexpression on the osteogenic differentiation of MC3T3-E1 cells. Exp. Ther. Med., 2015, 9(6), 2173-2179.
Armendáriz, B.G.; Bribian, A.; Pérez-Martínez, E.; Martínez, A.; de Castro, F.; Soriano, E.; Burgaya, F. Expression of semaphorin 4F in neurons and brain oligodendrocytes and the regulation of oligodendrocyte precursor migration in the optic nerve. Mol. Cell. Neurosci., 2012, 49(1), 54-67.
Goldstein, B.J.; Goss, G.M.; Choi, R.; Saur, D.; Seidler, B.; Hare, J.M.; Chaudhari, N. Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo. Development, 2016, 143(23), 4394-4404.
Liu, S.; Chen, X.; Wang, Y.; Li, L.; Wang, G.; Li, X.; Chen, H.; Guo, J.; Lin, H.; Lian, Q.Q.; Ge, R.S. A role of KIT receptor signaling for proliferation and differentiation of rat stem Leydig cells in vitro. Mol. Cell. Endocrinol., 2017, 444( 2017), 1-8.
Ding, H.; Zheng, S.; Garcia-Ruiz, D.; Hou, D.; Wei, Z.; Liao, Z.; Li, L.; Zhang, Y.; Han, X.; Zen, K.; Zhang, C.Y.; Li, J.; Jiang, X. Fasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16. Nat. Commun., 2016, 7( 2016), 11533.
Iyer, S.; Brooks, R.; Gumbleton, M.; Kerr, W.G. SHIP1-expressing mesenchymal stem cells regulate hematopoietic stem cell homeostasis and lineage commitment during aging. Stem Cells Dev., 2015, 24(9), 1073-1081.
Xia, Z.; Ma, P.; Wu, N.; Su, X.; Chen, J.; Jiang, C.; Liu, S.; Chen, W.; Ma, B.; Yang, X.; Ma, Y.; Weng, X.; Qiu, G.; Huang, S.; Wu, Z. Altered function in cartilage derived mesenchymal stem cell leads to OA-related cartilage erosion. Am. J. Transl. Res., 2016, 8(2), 433-446.
Kim, J.H.; Yoon, S.M.; Song, S.U.; Park, S.G.; Kim, W.S.; Park, I.G.; Lee, J.; Sung, J.H. Hypoxia suppresses spontaneous mineralization and osteogenic differentiation of mesenchymal stem cells via IGFBP3 up-regulation. Int. J. Mol. Sci., 2016, 17(9), 1389.
Fujitani, M.; Zhang, S.; Fujiki, R.; Fujihara, Y.; Yamashita, T. A chromosome 16p13.11 microduplication causes hyperactivity through dysregulation of miR-484/protocadherin-19 signaling. Mol. Psychiatry, 2017, 22(3), 364-374.
Shimada, I.S.; Acar, M.; Burgess, R.J.; Zhao, Z.; Morrison, S.J. Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells. Genes Dev., 2017, 31(11), 1134-1146.
Inoue, M.; Iwai, R.; Tabata, H.; Konno, D.; Komabayashi-Suzuki, M.; Watanabe, C.; Iwanari, H.; Mochizuki, Y.; Hamakubo, T.; Matsuzaki, F.; Nagata, K.I.; Mizutani, K.I. Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex. Development, 2017, 144(3), 385-399.
Choi, B.; Kang, S.S.; Kang, S.W.; Min, B.H.; Lee, E.J.; Song, D.H.; Kim, S.M.; Song, Y.; Yoon, S.Y.; Chang, E.J. Secretory clusterin inhibits osteoclastogenesis by attenuating M-CSF-dependent osteoclast precursor cell proliferation. Biochem. Biophys. Res. Commun., 2014, 450(1), 105-109.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [49 - 60]
Pages: 12
DOI: 10.2174/1389202919666181012145416
Price: $58

Article Metrics

PDF: 34
PRC: 1