Fibroblasts are the primary mesenchyme cell types that provide structural support during organ development and growth, and are the primary depositors of connective tissue matrix in response to injuries such as those occurring during skin scarring, tissue/organ fibrosis, systemic sclerosis, abdominal adhesions, just to name a few. Major efforts to study fibroblastic characteristics have centered on identifying surface markers that allow fibroblast purifications from tissues/organs. The glycoprotein CD90 is a widely expressed mesenchymal cell surface marker that is the subject of almost 1,000 publications (PubMed). It is present on mesenchymal stem cells (Dominici et al., 2006), fibroblasts of various organs (Kisselbach et al., 2009) and myofibroblasts (Saada et al., 2006), and in connective tissues throughout anatomic locations, including skin (Jahoda et al., 2003; Nazari et al., 2016), liver (Katsumata et al., 2017), heart (Nural-Guvener et al., 2014), eye (Khoo et al., 2008). CD90 is also found on mesenchyme within tumors that promote tumor growth (True et al., 2010). Based on CD90s expression on various mesenchyme cell types it has been considered as a defining fibroblastic marker (Katsumata et al., 2017).

Fibroblasts were originally described as a single cell type (Ramon y Cajal, 1900). However, recent studies by us and others have demonstrated that dermal fibroblasts are an assortment of phenotypically and functionally heterogeneous cells (Driskell et al., 2013; Rinkevich et al., 2015; Singhal et al., 2016; Jiang et al., 2018; Philippeos et al., 2018). The various dermal fibroblast subtypes have drastically diverged functions, during skin development, upon wounding and at homeostasis. These different dermal fibroblast cell types can be isolated based on unique gene expression or profiles of combination of surface markers such as CD26, Blimp1, Dlk1, Sca1 in mouse (Driskell et al., 2013; Rinkevich et al., 2015), and CD26, CD39, CD36, RGS5 in human (Philippeos et al., 2018). In addition, the α5 chain of collagen VI (COL6A5) is highly enriched in human papillary fibroblasts (Fitzgerald et al., 2008), and the discoidin-domain receptor 2 (DDR2) enriches for human cardiac fibroblasts (Goldsmith et al., 2004). CD90 alone therefore is not an accurate marker to define fibroblasts in general or its subtypes, because of the following reasons: