Variable expression of lineage regulators in differentiated stromal cells indicates distinct mechanisms of differentiation towards common cell fate

Abstract

Mesenchymal stem cells (MSCs) possess a multi-lineage differentiation capacity that makes them important players in the field of regenerative medicine. MSC populations derived from different tissues or donors have been shown to exhibit variable gene expression patterns. Further, it is widely acknowledged that MSC isolates are heterogeneous mixtures of cells at different developmental stages. However, the heterogeneity of expression of lineage regulators has not been linked to differentiation potential of different MSC populations towards mesenchymal lineages. Here, we analyzed variation of expression of differentiation markers across whole population and between single differentiating cells of multipotent stromal cell populations derived from adipose tissue (AdMSCs) and skin (FBs) of seven donors. The results of the analyses show that all cell populations exhibit similar differentiation potential towards adipocyte, osteoblast and chondrocyte lineages despite tissue type- and donor-specific variations of expression of differentiation-associated genes. Further, we detected variable expression of lineage regulators in individual differentiating cells. Together, our data indicate that single cells of stromal cell populations could use distinct molecular mechanisms to reach a common cell fate.

Keywords: AB; ACAN; ALP; APN; ARS; AdMSC; Alcian Blue; Alizarin Red S; C/EBP; CCAAT/enhancer-binding protein; Cell-to-cell variation; Col II; Differentiation; FABP4; FB; Gene expression; ORO; Oil Red O; PPARγ; Stromal cells; adiponectin; adipose-derived mesenchymal stem cell; aggrecan; alkaline phosphatase; collagen type II; fatty acid-binding protein 4; fibroblast; peroxisome proliferator-activated receptor gamma.