RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes

• DOI: 10.21203/rs.2.24666/v1
• Publication Date: 2020-02-27T02:22:01Z
• Authors: Satoru Onizuka; Yasuharu Yamazaki; Sung-Joon Park; Takayuki Sugimoto; Yumiko Sone; Sebastian Sjöqvist; Michihiko Usui; Akira Takeda; Kenta Nakai; Keisuke Nakashima; Takanori Iwata
• Keywords: 0301 basic medicine; Iliac bone; Maxillofacial bone; RNA-sequencing; Mandible; QH426-470; Ilium; 03 medical and health sciences; Exome Sequencing; Genetics; Maxilla; Humans; Gene Regulatory Networks; Multipotent mesenchymal stromal cells; Cells, Cultured; Cell Proliferation; Homeodomain Proteins; 0303 health sciences; Sequence Analysis, RNA; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Cell Differentiation; Mesenchymal Stem Cells; HOX genes; Gene Expression Regulation; Organ Specificity; TP248.13-248.65; Periodontal ligament; Biotechnology; Research Article

Abstract Background Multipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin.Results We isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandibular (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of human embryonic stem cells (ESCs) and several types of MSCs (periodontal ligament-derived MSCs, bone marrow-derived MSCs, and ESCs-derived MSCs) from the Sequence Reads Archive and analyze the transcriptome profile. We found that MSCs derived from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those derived from other tissues were HOX-positive. We also identified that MSX1, LHX8, and BARX1 , an essential regulator of craniofacial development, were strongly expressed in maxillofacial tissue-derived MSCs. Although MSCs may be divided into two distinct groups, the cells originated from over the neck or not, on the basis of differences in gene expression profile, the expression patterns of all CD antigen genes were similar among different type of MSCs, except for ESCs.Conclusions Our findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain an original tissue memory about the developmental process, including gene expression profiles. This could have an important impact when choosing an appropriate cell source for regenerative therapy using MSCs.