Comparative transcriptomic analysis of human mesenchymal stem cells derived from dental pulp and adipose tissues

Atsushi Terunuma,Yosuke Sakaguchi,Tsubasa Takane,Keisuke Ashiba,Hiroshi Takahashi

doi:10.46582/jsrm.1501003

Abstract

Objective: Mesenchymal stem cells (MSCs) have been isolated from various human tissues. Although they share cardinal stem cell features of self-renewal and multi-potency, they also seem to possess distinct characteristics depending on the tissue types they originated from. When developing stem cell-based therapies, MSCs with the most desirable characteristics should be chosen. However, our knowledge on tissue type-specific characteristics of MSCs is limited. Here, we comparatively studied the gene expression profiles of MSCs from different tissue types, and predicted target diseases suitable for each type of MSCs. Methods: We harvested MSCs from human dental pulp and adipose tissue specimens and subjected them to gene expression microarray analysis. Characteristic gene expression signatures of the MSCs from each tissue type were identified using gene-annotation enrichment analysis. Results: Dental pulp-derived MSCs exhibited gene expression signatures of neuronal growth, while adipose tissue-derived MSCs exhibited signatures of angiogenesis and hair growth. MSCs from each tissue type expressed a discrete set of genes encoding secretory peptides, which may function as paracrine factors. Conclusions: MSCs derived from different tissue types demonstrated distinct gene expression signatures, which are suggestive of target diseases in clinical applications of the MSCs and stem cell-conditioned media. By expanding the analysis to MSCs from a wide range of tissue types, and by employing multiple omics approaches, a catalogue of MSCs and therapeutic targets can be generated.

Highlights

Human mesenchymal stromal cells (MSCs) play pivotal roles in repairing damaged tissues; they migrate to sites of tissue damage, secrete soluble factors in a paracrine fashion to enhance wound healing, and sometimes differentiate into certain cell types to reconstruct tissues
As shown in an Multi-dimensional scaling (MDS) plot (Figure 1A), all 13 MSCs samples were grossly different from fibroblasts
Seven DP-hMSCs samples formed a tight cluster (Figure 1A; circled in blue), indicating that DP-hMSCs share very similar gene expression profiles even if they originated from independent donors

Summary

Introduction

Human mesenchymal stromal cells (MSCs) play pivotal roles in repairing damaged tissues; they migrate to sites of tissue damage, secrete soluble factors in a paracrine fashion to enhance wound healing, and sometimes differentiate into certain cell types to reconstruct tissues. MSCs, as well as stem cell-conditioned media and exosomes contained therein, have been used to treat diverse disorders[1], including cerebral infarction[2], spinal cord injury[3,4,5], diabetes mellitus[6], obesity[7], atopic dermatitis[8], inflammatory bowel disease[9] and liver disorders[10] . RNA sequencing revealed distinctively different gene expression profiles in MSCs from bone marrow, adipose tissue, and palatine tonsils[11].

Results

Conclusion