title: Small RNA and RNA-IP Sequencing Identifies and Validates Novel MicroRNAs in Human Mesenchymal Stem Cells.
abstract: Organ regeneration therapies using multipotent mesenchymal stem cells (MSCs) are currently being investigated for a variety of common complex diseases. Understanding the molecular regulation of MSC biology will benefit regenerative medicine. MicroRNAs (miRNAs) act as regulators in MSC stemness. There are approximately 2500 currently known human miRNAs that have been recorded in the miRBase v21 database. In the present study, we identified novel microRNAs involved in MSC stemness and differentiation by obtaining the global microRNA expression profiles (miRNomes) of MSCs from two anatomical locations bone marrow (BM-MSCs) and umbilical cord Wharton's jelly (WJ-MSCs) and from osteogenically and adipogenically differentiated progenies of BM-MSCs. Small RNA sequencing (smRNA-seq) and bioinformatics analyses predicted that 49 uncharacterized miRNA candidates had high cellular expression values in MSCs. Another independent batch of Ago1/2-based RNA immunoprecipitation (RNA-IP) sequencing datasets validated the existence of 40 unreported miRNAs in cells and their associations with the RNA-induced silencing complex (RISC). Nine of these 40 new miRNAs were universally overexpressed in both MSC types; nine others were overexpressed in differentiated cells. A novel miRNA (UNI-118-3p) was specifically expressed in BM-MSCs, as verified using RT-qPCR. Taken together, this report offers comprehensive miRNome profiles for two MSC types, as well as cells differentiated from BM-MSCs. MSC transplantation has the potential to ameliorate degenerative disorders and repair damaged tissues. Interventions involving the above 40 new microRNA members in transplanted MSCs may potentially guide future clinical applications.
authors.affiliation: 1 Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital , Hsinchu, Taiwan .
authors.forename: Chin-Han
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: 2 Institute of Microbiology and Immunology.
authors.forename: Ko-Hsun
authors.initials: KH
authors.lastname: Liao
authors.affiliation: 1 Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital , Hsinchu, Taiwan .
authors.forename: Chuan-Chi
authors.initials: CC
authors.lastname: Shih
authors.affiliation: 1 Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital , Hsinchu, Taiwan .
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Chan
authors.affiliation: 2 Institute of Microbiology and Immunology.
authors.forename: Jui-Yu
authors.initials: JY
authors.lastname: Hsieh
authors.affiliation: 2 Institute of Microbiology and Immunology.
authors.forename: Cheng-Fong
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: 2 Institute of Microbiology and Immunology.|3 VGH-YM Genome Research Center, National Yang-Ming University , Taipei, Taiwan .|4 Departments of Education and Research, Taipei City Hospital , Taipei, Taiwan .
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: 1 Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital , Hsinchu, Taiwan .
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex