Multiple coagulation factor deficiency protein 2 contains the ability to support stem cell self‐renewal

Abstract

Defects in multiple coagulation factor deficiency protein 2 (MCFD2) are a cause of factor V and factor VIII combined deficiency type 2 (F5F8D). MCFD2 was also suggested to play an important role as an autocrine/paracrine factor in maintaining neural stem cell potential. The current work provided direct evidence that both amphibian and human MCFD2 can maintain stem cell pluripotency or stemness of rhesus monkey embryonic stem cells (rESCs) as basic fibroblast growth factor 2 (FGF-2) does. In most cases, MCFD2 had identical effects on stem cells as FGF-2. We investigated the possible mechanism of MCFD2 to support stem cell pluripotency by highlighting the effects of MCFD2 and FGF-2 on several signaling pathways in rESCs, namely MAPK, TGF-β, Wnt, and Akt, and 3 core transcriptional factors (Oct4, Nanog, and Sox2). In addition, some features of signaling pathways (MAPK and Akt), which are different from human embryonic stem cells (hESCs) and mouse embryonic stem cells (mESCs), are found in rESCs, indicating that primate ESCs have unique signaling mechanisms. These results may shed light on the biological roles of MCFD2, the conserved protein family distributed in both vertebrates and invertebrates. The ability to support stem cell self-renewal may be the general function of the conserved protein family.