Impact of tissue-specific stem cells on lineage-specific differentiation: a focus on the musculoskeletal system

Abstract

Tissue-specific stem cells are found throughout the body and, with proper intervention and environmental cues, these stem cells exercise their capabilities for differentiation into several lineages to form cartilage, bone, muscle, and adipose tissue in vitro and in vivo. Interestingly, it has been widely demonstrated that they do not differentiate with the same efficacy during lineage-specific differentiation studies, as the tissue-specific stem cells are generally more effective when differentiating toward the tissues from which they were derived. This review focuses on four mesodermal lineages for tissue-specific stem cell differentiation: adipogenesis, chondrogenesis, myogenesis, and osteogenesis. It is intended to give insight into current multilineage differentiation and comparative research, highlight and contrast known trends regarding differentiation, and introduce supporting evidence which demonstrates particular tissue-specific stem cells' superiority in lineage-specific differentiation, along with their resident tissue origins and natural roles. In addition, some epigenetic and transcriptomic differences between stem cells which may explain the observed trends are discussed.

Figure 1

Adult stem cells can be derived from various tissues in the body. These viable and undifferentiated stem cell populations can be expanded in vitro and induced to undergo lineage-specific differentiation for chondrogenesis (C), osteogenesis (O), myogenesis (M), or adipogenesis (A). Although the cells may appear similar in morphology upon harvest, they are anything but identical. From the data presented in the section “Tissue-Specific Stem Cells Benefiting Lineage-Specific Differentiation”, the efficacy of ASCs in lineage-specific differentiation is greatly affected by the type of resident tissue from which they are harvested. In the heatmap, the differentiation capacity is visualized by color ranging from low differentiation (blue) to high differentiation (red).

Figure 2

Epigenetic determination of niche-specific lineage preference. CpG methylation of promoters creates a permissive, but non-predictive state, while non-promoter CpG methylation, histone modifications, and differentially expressed miRNAs may combine to determine lineage preference.