Characterization of a novel umbilical cord lining cell with CD227 positivity and unique pattern of P63 expression and function.

Umbilical cord tissue is gaining attention as a novel source of multipotent stem cells because it is easily obtainable, ethically acceptable and the cells are immunologically naïve. In this study, we have isolated and characterized a new cell type expressing MUCIN1 (CD227) from human umbilical cord lining which we termed MUCIN-expressing Cord Lining Epithelial Cell (CLEC-muc). We found that CLEC-muc is highly proliferative and had significant clonogenic ability. These cells express embryonic stem cell markers OCT-4, NANOG, SSEA-4, REX1 and SOX2. Despite the abundant expression of epithelial cell marker MUCIN1 and cytokeratins, this population is also positive to the mesenchymal stem cell (MSC) marker CD166. CLEC-muc is unique in p63 expression that shuttles from the cytoplasm to the nucleus over time in culture. To understand p63 regulation and function in CLEC-muc, cells were treated with BMP4, a potent morphogen that plays a role in epidermal differentiation via p63 upregulation in ES cell and subsequent analyses were done. We found that BMP4 does not alter cytoplasmic expression of p63 that promotes cell proliferation. However, it increases nuclear p63 expression together with several other epithelial-associated genes such as GATA3, JAGGED1, NOTCH1, HES1 and IKKα. BMP4 has also been found to weakly induce deltaNp63 expression in CLEC-muc. Our results suggest that CLEC-muc is a novel stem cell-like population that can be further differentiated by BMP4 to generate specific cell-types probably destined to form non-keratinized epithelia.