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EMBRYONIC STEM CELLS

Disruption of Apical-Basal Polarity of Human Embryonic Stem Cells Enhances Hematoendothelial Differentiation

Departments of ^aCell and Tissue Biology,
^bAnatomy, and
^cPharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA;
^dLawrence Berkeley National Laboratory, Berkeley, California, USA;
^eStem Cell Bank, Prince Felipe Research Center and Instituto Valenciano de Infertilidad (IVI) Foundation, University of Valencia, Valencia, Spain;
^fStemLifeLine, Inc., San Carlos, California, USA

Key Words. Human embryonic stem cells • Inner cell mass • Apical-basal polarity • Embryoid body formation • Hematoendothelial differentiation

Correspondence: Susan J. Fisher, Ph.D., 513 Parnassus, HSE 1619, Box 0512, University of California San Francisco, San Francisco, California 94143-0512, USA. Telephone: (415) 476-5297; Fax: (415) 502-7338; e-mail: sfisher{at}cgl.ucsf.edu

Received March 28, 2007; accepted for publication June 7, 2007.
First published online in STEM CELLS EXPRESS   June 14, 2007.



During murine development, the formation of tight junctions and acquisition of polarity are associated with allocation of the blastomeres on the outer surface of the embryo to the trophoblast lineage, whereas the absence of polarization directs cells to the inner cell mass. Here, we report the results of ultrastructural analyses that suggest a similar link between polarization and cell fate in human embryos. In contrast, the five human embryonic stem cell (hESC) lines displayed apical-basal, epithelial-type polarity with electron-dense tight junctions, apical microvilli, and asymmetric distribution of organelles. Consistent with these findings, molecules that are components of tight junctions or play regulatory roles in polarization localized to the apical regions of the hESCs at sites of cell-cell contact. The tight junctions were functional, as shown by the ability of hESC colonies to exclude the pericellular passage of a biotin compound. Depolarization of hESCs produced multilayered aggregates of rapidly proliferating cells that continued to express transcription factors that are required for pluripotency at the same level as control cells. However, during embryoid body formation, depolarized cells differentiated predominantly along mesenchymal lineage and spontaneously produced hematoendothelial precursors more efficiently than control ESC. Our findings have numerous implications with regard to strategies for deriving, propagating, and differentiating hESC.

Disclosure of potential conflicts of interest is found at the end of this article.

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