Hair follicle stem cells (HFSCs) play a significant role in hair development. miR-1 has been reported as an important regulatory factor that affects hair follicle growth and development, but its regulatory mechanism on HFSC development remains unknown. In this study, the molecular mechanism of miR-1 in regulating HFSC proliferation and differentiation was investigated. High-throughput RNA-seq and integrated analysis were performed to identify differentially transcribed mRNAs and microRNAs (miRNAs) in HFSCs co-cultured with dermal papilla cells (named dHFSCs) and control HFSCs. We then determined the molecular function of miR-1 in HFSCs. Compared with HFSCs, 13 differentially transcribed miRNAs were identified in dHFSCs. The in vitro results indicated that the overtranscription of miR-1 inhibited HFSC proliferation, but enhanced HFSC differentiation by targeting IGF1R and LEF1 genes. This study provides new insights into the molecular mechanisms of HFSC development. Approval ID (2014ZX08008-002).
Get full access to this article
View all access options for this article.
References
1.
AhmedM.I., MajidA., EmelianovV.U., KrzysztofP., AnkitP., SharovA.A., et al. (2014). MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway. J Cell Biol, 207, 549–567.
2.
CaiB., ZhengY., MaS., XingQ., WangX., YangB., et al. (2018). Long non-coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway. Mol Med Rep, 17, 5477–5483.
3.
CédricB., and ElaineF. (2014). Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration. Science, 344, 1242281.
4.
ChenC., WangD., MoshaveriniaA., LiuD., KouX., YuW., et al. (2017). Mesenchymal stem cell transplantation in tight-skin mice identifies miR-151-5p as a therapeutic target for systemic sclerosis. Cell Res, 27, 559–577.
5.
DevosM., MogilenkoD.A., FleuryS., GilbertB., BecquartC., QuemenerS., et al. (2019). Keratinocyte expression of A20/TNFAIP3 controls skin inflammation associated with atopic dermatitis and psoriasis. J Invest Dermatol, 139, 135–145.
6.
DriskellR.R., CarlosC., MichaelR., and WattF.M. (2011). Hair follicle dermal papilla cells at a glance. J Cell Sci, 124, 1179–1182.
7.
DuK.T., DengJ.Q., HeX.G., LiuZ.P., PengC., and ZhangM.S. (2018a). MiR-214 regulates the human hair follicle stem cell proliferation and differentiation by targeting EZH2 and Wnt/β-catenin signaling way in vitro. Tissue Eng Regen Med, 15, 341–350.
8.
DuP., PirouzM., ChoiJ., HuebnerA.J., ClementK., MeissnerA., et al. (2018b). An intermediate pluripotent state controlled by microRNAs is required for the naive-to-primed stem cell transition. Cell Stem Cell, 22, 851.e855–864.e855.
9.
ElaineF. (2007). Scratching the surface of skin development. Nature, 445, 834.
10.
FriedländerM.R., MackowiakS.D., LiN., ChenW., and RajewskyN. (2012). miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res, 40, 37–52.
11.
Gallo-OllerG., OrdoñezR., and DotorJ. (2018). A new background subtraction method for Western blot densitometry band quantification through image analysis software. J Immunol Methods, 457, 1–5.
12.
GaoY., WangX., YanH., ZengJ., MaS., NiuY., et al. (2016). Comparative transcriptome analysis of fetal skin reveals key genes related to hair follicle morphogenesis in cashmere goats. PLoS One, 11, e0151118.
13.
Griffiths-JonesS., SainiH.K., van DongenS., and EnrightA.J. (2008). miRBase: tools for microRNA genomics. Nucleic Acids Res, 36, D154–D158.
14.
HeJ.T., HuangH.Y., QuD., XueY., ZhangK.K., XieX.L., et al. (2018). CXCL1 and CXCR2 as potential markers for vital reactions in skin contusions. Forensic Sci Med Pathol, 14, 1–6.
15.
HeX., ChaoY., ZhouG., and ChenY. (2016). Fibroblast growth factor 5-short (FGF5s) inhibits the activity of FGF5 in primary and secondary hair follicle dermal papilla cells of cashmere goats. Gene, 575, 393–398.
16.
HoffmanR.M. (2006). The pluripotency of hair follicle stem cells. Cell Cycle, 5, 232–233.
17.
KandybaE., and KobielakK. (2014). Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling. Stem Cells, 32, 886–901.
18.
KerteszM., IovinoN., UnnerstallU., GaulU., and SegalE. (2007). The role of site accessibility in microRNA target recognition. Nat Genet, 39, 1278–1284.
19.
KimD., PerteaG., TrapnellC., PimentelH., KelleyR., and SalzbergS.L. (2013). TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol, 14, R36.
20.
KrügerJ., and RehmsmeierM. (2006). RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res, 34, W451–W454.
21.
LangmeadB., TrapnellC., PopM., and SalzbergS.L. (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol, 10, R25.
22.
LiA., JiaP., MallikS., FeiR., YoshiokaH., SuzukiA., et al. (2019). Critical microRNAs and regulatory motifs in cleft palate identified by a conserved miRNA–TF–gene network approach in humans and mice. Brief Bioinform, 21, 1465–1478.
23.
LittleJ.C., RedwoodK.L., GrangerS.P., and JenkinsG. (2010). In vivo cytokine and receptor gene expression during the rat hair growth cycle. Analysis by semi-quantitative RT-PCR. Exp Dermatol, 5, 202–212.
24.
LiuJ.P., BakerJ., PerkinsA.S., RobertsonE.J., and EfstratiadisA. (1993). Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell, 75, 59–72.
25.
LoveM.I., HuberW., and AndersS. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol, 15, 550.
MadaanA., VermaR., SinghA.T., and JaggiM. (2018). Review of hair follicle dermal papilla cells as in vitro screening model for hair growth. Int J Cosmet Sci, 40, 429–450.
28.
MaoX., CaiT., OlyarchukJ.G., and WeiL. (2005). Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary. Bioinformatics, 21, 3787–3793.
29.
MardaryevA.N., AhmedM.I., VlahovN.V., FessingM.Y., GillJ.H., SharovA.A., et al. (2010). Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle. FASEB J, 24, 3869–3881.
30.
MarioniJ.C., MasonC.E., ManeS.M., StephensM., and GiladY. (2008). RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res, 18, 1509–1517.
MerrillB.J., GatU., DasGuptaR., and FuchsE. (2001). Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev, 15, 1688–1705.
33.
OjehN., PastarI., Tomic-CanicM., and StojadinovicO. (2015). Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci, 16, 25476–25501.
34.
PandiniG., WurchT., and AklaB. (2007). Functional responses and in vivo anti-tumour activity of h7C10: a humanised monoclonal antibody with neutralising activity against the insulin-like growth factor-1 (IGF-1) receptor and insulin/IGF-1 hybrid receptors. Eur J Cancer, 43, 1318–1327.
35.
PausR., and FoitzikK. (2010). In search of the “hair cycle clock”: a guided tour. Differentiation, 72, 489–511.
36.
ReynoldsA.J., OliverR.F., and JahodaC.A. (1991). Dermal cell populations show variable competence in epidermal cell support: stimulatory effects of hair papilla cells. J Cell Sci, 98 (Pt 1), 75–83.
37.
ShenQ., YuW., FangY., YaoM., and YangP. (2017). Beta-catenin can induce hair follicle stem cell differentiation into transit-amplifying cells through c-myc activation. Tissue Cell, 49, 28.
38.
StewartC.E., and RotweinP. (1996). Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev, 76, 1005–1026.
39.
TudoritaT., GeraldineG., ValentinaG., CedricB., LowryW.E., MichaelR., et al. (2004). Defining the epithelial stem cell niche in skin. Science, 303, 359–363.
40.
Van GenderenC., OkamuraR.M., FariñasI., QuoR.G., ParslowT.G., BruhnL., et al. (1994). Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev, 8, 2691–2703.
41.
WenM., ShenY., ShiS., and TangT. (2012). miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments. BMC Bioinform, 13, 140.
42.
WilliamsH., CromptonR.A., ThomasonH.A., CampbellL., SinghG., McbainA.J., et al. (2017). Cutaneous Nod2 expression regulates the skin microbiome and wound healing in a murine model. J Invest Dermatol, 137, S0022202X17316615.
43.
WuZ., FuY., CaoJ., YuM., TangX., and ZhaoS. (2014). Identification of differentially expressed miRNAs between white and black hair follicles by RNA-sequencing in the goat (Capra hircus). Int J Mol Sci, 15, 9531–9545.
44.
XuejuanL., LeiS., JinyuL., ShichaoW., XiaohuaT., XiaoguangB., et al. (2013). miR-18b inhibits TGF-β1-induced differentiation of hair follicle stem cells into smooth muscle cells by targeting SMAD2. Biochem Biophys Res Commun, 438, 551–556.
45.
YanH., GaoY., DingQ., LiuJ., LiY., JinM., et al. (2019). Exosomal micro RNAs derived from dermal papilla cells mediate hair follicle stem cell proliferation and differentiation. Int J Biol Sci, 15, 1368–1382.
YoungM.D., WakefieldM.J., SmythG.K., and OshlackA. (2010). Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol, 11, R14.
48.
YuanC., WangX., GengR., HeX., QuL., and ChenY. (2013). Discovery of cashmere goat (Capra hircus) microRNAs in skin and hair follicles by Solexa sequencing. BMC Genom, 14, 511.
49.
ZhangB., TsaiP.C., Gonzalez-CeleiroM., ChungO., BoumardB., PerdigotoC.N., et al. (2016). Hair follicles' transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog. Genes Dev, 30, 2325.
50.
ZhangY., YuJ., ShiC., HuangY., WangY., YangT., et al. (2013). Lef1 contributes to the differentiation of bulge stem cells by nuclear translocation and cross-talk with the Notch signaling pathway. Int J Med Sci, 10, 738–746.
ZhouG.X., YuanC., HeX.L., KangD.J., WangX.L., and ChenY.L. (2017). Effect of miR-125b on dermal papilla cells of goat secondary hair follicle. Electron J Biotechnol, 25, 64–69.
53.
ZhouL., ChenJ., LiZ., LiX., HuX., HuangY., et al. (2010). Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma. PLoS One, 5, e15224.
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
