CD marker expression profiles of human embryonic stem cells and their neural derivatives, determined using flow-cytometric analysis, reveal a novel CD marker for exclusion of pluripotent stem cells

Abstract

Human embryonic stem cells (hESCs) are pluripotent cells that can differentiate into neural cell lineages. These neural populations are usually heterogeneous and can contain undifferentiated pluripotent cells that are capable of producing teratomas in cell grafts. The characterization of surface protein profiles of hESCs and their neural derivatives is important to determine the specific markers that can be used to exclude undifferentiated cells from neural populations. In this study, we analyzed the cluster of differentiation (CD) marker expression profiles of seven undifferentiated hESC lines using flow-cytometric analysis and compared their profiles to those of neural derivatives. Stem cell and progenitor marker CD133 and epithelial adhesion molecule marker CD326 were more highly expressed in undifferentiated hESCs, whereas neural marker CD56 (NCAM) and neural precursor marker (chemokine receptor) CD184 were more highly expressed in hESC-derived neural cells. CD326 expression levels were consistently higher in all nondifferentiated hESC lines than in neural cell derivatives. In addition, CD326-positive hESCs produced teratomas in SCID mouse testes, whereas CD362-negative neural populations did not. Thus, CD326 may be useful as a novel marker of undifferentiated hESCs to exclude undifferentiated hESCs from differentiated neural cell populations prior to transplantation.

Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells

“…The finding that CD56 is also up-regulated during mesodermal differentiation of hESCs suggests that CD56 is likely to be fundamental to the reorganization of cell assembly rather than specific to mesodermal commitment per se. Expression of CD56 has also been documented in neuroectodermal progenitors derived from hESCs (20). Thus, the significance of surface markers is context specific and may differ dramatically in different culture conditions.…”

Expression Profile of the Stem Cell Markers in Human Hertwig’s Epithelial Root Sheath/Epithelial Rests of Malassez Cells

“…ABCG2 (drug-resistance ABC transporter) (Ding et al, 2010), ΔNp63 (truncated dominant-negative isoform of p63) (Barbareschi et al, 2001;Parsa et al, 1999;Pellegrini et al, 2001;Yang et al, 1998;, and p75 (a low-affinity neurotrophin receptor) (Nakamura et al, 2007;Okumura et al, 2003) are widely accepted as epithelial stem cell markers. EpCAM is a pan-epithelial differentiation antigen that is expressed in undifferentiated pluripotent stem cells; it is a calcium-independent cell adhesion molecule that is related to increased epithelial proliferation and negatively correlates with cell differentiation (Balzar et al, 1999;Sundberg et al, 2009). Bmi-1 has an essential role in embryogenesis regulation of the cell cycle and lymphopoiesis (Jacobs and van Lohuizen, 1999;Raaphorst et al, 2001), and it is expressed in hematopoietic stem cells and in stem cells from other tissues (Molofsky et al, 2003;.…”

Crystal structure and its bearing towards an understanding of key biological functions of EpCAM

“…A member of this diverse group of proteins is the epithelial cell adhesion molecule (EpCAM, CD326), a type I transmembrane (TM) glycoprotein of the small GA733 protein family named after the monoclonal antibody raised to the human gastric adenocarcinoma line 1 . In contrast to low expression in normal simple epithelia, EpCAM is frequently expressed at high levels in various epithelial cancers (carcinomas) 2 and in undifferentiated human embryonic stem cells 3,4 . Elevated EpCAM levels in carcinomas are exploited by several anti-tumor approaches, which deploy EpCAM for drug targeting (reviewed in ref.…”