Original article from STEM CELLS
“Cellular Heterogeneity During Embryonic Stem Cell Differentiation to Epiblast Stem Cells Is Revealed by the ShcD/RaLP Adaptor Protein”
The Shc (Src homolog and collagen homolog) family of adaptor proteins is a crucial linker of a wide range of receptors to their downstream effectors (Pelicci et al). Four Shc proteins (ShcA isoforms p52 and p46, p66ShcA and ShcC) had previously been identified in mammals and implicated in distinct signaling pathways, but now a 4th family member and 5th protein, ShcD/RaLP, has been identified. Studies have found ShcD to be expressed in the neuromuscular junction, mediating muscle-specific kinase signaling (Jones et al), in melanocytes, implicated in mitogen-activated protein kinase (MAPK) signalling (Fagiani et al), and in the brain (Jones et al), and has been reported to be involved in the metastatic progression of melanoma. Now, in a report in Stem Cells, researchers from the laboratory of Luisa Lanfrancone at the Department of Experimental Oncology, European Institute of Oncology, Milan, Italy have found ShcD to be an important modulator in the switch of key pathways involved in determining EpiSC identity; ShcD is transiently upregulated during early differentiation of ESCs, corresponding to the ESC to epiblast stem cells (EpiSCs) transition, while loss of ShcD perturbs the commitment process (Turco et al). Additionally, loss of ShcD in ESCs increased the heterogeneity of cells during both differentiation and EpiSC determination as measured through the loss of Oct4 and gain of Cdx2 in distinct subpopulations of cells.