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

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 mandible (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 analyzed 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.

Elucidation of adipogenic differentiation regulatory mechanism in human maxillary/mandibular bone marrow-derived stem cells

“…Our previous study revealed that the osteogenic potential of MBMSCs was similar to that of iliac bone marrow-derived MSCs (IBMSCs); however, MBMSCs scarcely differentiated into adipocytes [5]. Consistent with our study, other groups have also reported that MBMSCs exhibit lower adipogenic differentiation potential than that exhibited by IBMSCs [7,10]. However, the mechanisms through which the differentiation of MBMSCs is regulated remain unclear.…”

“…Most of the bone tissue is derived from the mesoderm, whereas the craniofacial bone, including the maxillary/mandibular bone, is derived from the neural crest [6]. MSCs isolated from the orofacial region and iliac crest have been reported to exhibit site-speci c characteristics owing to the differences in embryological origins [7][8][9][10].…”

Characterization and Study of Gene Expression Profiles of Human Periodontal Mesenchymal Stem Cells in Spheroid Cultures by Transcriptome Analysis

“…These data suggest that the gene profiles in spheroids with different MSCs are somewhat consistent. In our previous transcriptome analysis of bone marrow-derived MSCs and PDL-derived MSCs, the expression of the HOX gene differed between the two MSCs [ 23 ]. In other words, MSCs derived from different anatomical sites have marked differences in gene expression and positional memory, although they meet the same general characterization criteria.…”

Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability

“…For example, craniofacial bones are generated by neural crest-derived MSCs, but the axial and appendicular bones are derived from paraxial and lateral mesoderm (LM)-derived MSCs, respectively ( Olsen et al, 2000 ; Isern et al, 2014 ). Furthermore, maxilla-derived MSCs are negative for homeodomain transcription factor (HOX) gene expression, while ilium-derived MSCs highly express HOX genes and exhibit superior differentiation to chondrocytes compared with maxilla- and mandible-derived MSCs ( Matsubara et al, 2005 ; Onizuka et al, 2020 ), further suggesting that MSCs of different origins possess variable functions. The above evidence indicates that the functional heterogeneity of MSCs may be partially due to their undefined developmental origins.…”