title: Transcriptional profiling reveals crosstalk between mesenchymal stem cells and endothelial cells promoting prevascularization by reciprocal mechanisms.
abstract: Mesenchymal stem cells (MSCs) show great promise in blood vessel restoration and vascularization enhancement in many therapeutic situations. Typically, the co-implantation of MSCs with vascular endothelial cells (ECs) is effective for the induction of functional vascularization in vivo, indicating its potential applications in regenerative medicine. The effects of MSCs-ECs-induced vascularization can be modeled in vitro, providing simplified models for understanding their underlying communication. In this article, a contact coculture model in vitro and an RNA-seq approach were employed to reveal the active crosstalk between MSCs and ECs within a short time period at both morphological and transcriptional levels. The RNA-seq results suggested that angiogenic genes were significantly induced upon coculture, and this prevascularization commitment might require the NF-κB signaling. NF-κB blocking and interleukin (IL) neutralization experiments demonstrated that MSCs potentially secreted IL factors including IL1β and IL6 to modulate NF-κB signaling and downstream chemokines during coculture. Conversely, RNA-seq results indicated that the MSCs were regulated by the coculture environment to a smooth muscle commitment within this short period, which largely induced myocardin, the myogenic co-transcriptional factor. These findings demonstrate the mutual molecular mechanism of MSCs-ECs-induced prevascularization commitment in a quick response.
authors.affiliation: 1 School of Life Sciences, Tsinghua University , Beijing, China .
authors.forename: Junxiang
authors.initials: J
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Ruifang
authors.initials: R
authors.lastname: Teng
authors.forename: Qian
authors.initials: Q
authors.lastname: Guan
authors.forename: Jidong
authors.initials: J
authors.lastname: Lang
authors.forename: Jianhuo
authors.initials: J
authors.lastname: Fang
authors.forename: Haizhou
authors.initials: H
authors.lastname: Long
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D002449:Cell Aggregation; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic; D059467:Transcriptome
chemical_list: D042501:Angiogenic Proteins; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B