CD also known as CUB domain containing

CD318, also known as CUB domain-containing protein 1, acts as a substrate for Src family kinases and is associated with the metastatic potential of cancer catalase inhibitor (Wortmann et al., 2009). In addition to cancer cells, CD318 has been reported to be present in several stem/progenitor populations such as hematopoietic stem/progenitor cells, mesenchymal stem cells, and neural progenitor cells (Buhring et al., 2004; Conze et al., 2003; Takeda et al., 2010). We reported here that CD318 is also expressed on human myogenic progenitors with an expression pattern similar to that of CD82. However, expression of CD318 was diminished in commercially available myoblasts and undetectable in iPSC-derived cells. Although the exact reason for the downregulation of CD318 is currently unknown, the oxygen concentration used in those cultures differed from that in our culture condition. We used a hypoxic condition for cell culture, but commercially available myoblasts or iPSCs were cultured in a normoxic condition. Because expression of CD318 is induced by hypoxia (Cao et al., 2015; Emerling et al., 2013; Razorenova et al., 2011), a different oxygen concentration might lead to a difference in CD318 expression. CD201, also known as endothelial protein C receptor, is a type 1 transmembrane glycoprotein expressed in the endothelium of large blood vessels and also in many other cell types (Mohan Rao et al., 2014). Its well-known function is anticoagulation. Our analysis revealed that CD201 is specifically expressed in mesenchymal progenitors but not in myogenic satellite cells within human skeletal muscle. While previously reported mesenchymal markers such as CD15 (Lecourt et al., 2010; Pisani et al., 2010a), CD34 (Pisani et al., 2010b; Vauchez et al., 2009), CD73 (Downey et al., 2015), CD90 (Downey et al., 2015), and CD105 (Downey et al., 2015) were distributed equally on both cultured myogenic and mesenchymal progenitors, our comprehensive analysis identifies one of the most powerful markers, which is equivalent to PDGFRα and can distinguish mesenchymal progenitors from myogenic cells. We also found that human mesenchymal progenitors highly express PAR1, a co-receptor of CD201. CD201 is selectively expressed in HSCs (Balazs et al., 2006), and CD201-PAR1 signaling has been recently shown to regulate the retention and recruitment of HSCs within the bone marrow microenvironment (Gur-Cohen et al., 2015). We showed in this study that stimulation of CD201-PAR1 signaling in mesenchymal progenitors leads to enhanced adipogenesis by activating the Akt and Erk pathway. Thus, our study further unveils an additional function of CD201, which is traditionally recognized as a coagulation-related factor, as a regulator of stem/progenitor cell function.
Experimental Procedures
Author Contributions
Acknowledgments We thank K. Ono for proofreading the paper. This work was supported by AMED Research Center Network for Realization of Regenerative Medicine, AMED Health and Labor Sciences Research Grants for Comprehensive Research on Persons with Disabilities, Japan Foundation for Aging and Health, JSPS KAKENHI Grant Number 15K12675, Astellas Pharma, and the 24th General Assembly of the Japanese Association of Medical Sciences.
Introduction Spermatogonial stem cells (SSCs) are the founder cell population of spermatogenesis (de Rooij and Russell, 2000; Meistrich and van Beek, 1993). Although their number in testes is very small (0.02%–0.03% of total germ cells), they are the only stem cells in the germline that have the unique ability to undergo self-renewal division to produce numerous progenitor cells. SSCs are thought to develop from gonocytes in the neonatal testis during the perinatal stage (Shinohara et al., 2001). SSCs rapidly expand their number during sexual maturation and maintain a constant population size in adults. The SSC population size is determined based on the number of niches (Oatley et al., 2011), which likely develop through complex interactions among Sertoli cells, Leydig cells, peritubular myoid cells, and macrophages (DeFalco et al., 2015; Meng et al., 2000; Oatley et al., 2009; Spinnler et al., 2010). Sexual maturation is accompanied by dynamic changes in hormonal milieu, and development of these cell types is influenced by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secreted from the pituitary gland. However, little is known regarding the roles of these hormones in SSC and niche development.