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Primary Differentiation in the Human Blastocyst: Comparative Molecular Portraits of Inner Cell Mass and Trophectoderm Cells

^a Max-Planck Institute for Molecular Genetics (Department of Vertebrate Genomics), Berlin, Germany;
^b Reproduction and Early Development Research Group, Department of Obstetrics and Gynaecology, University of Leeds, Leeds, W. Yorkshire, United Kingdom;
^c Center for Reproductive Medicine & Infertility, Weill Medical College, Cornell University, New York, New York, USA

Key Words. Preimplantation development • Blastocyst • Inner cell mass • Trophectoderm • Pluripotency • Embryonic stem cells • Trophoblastic stem cells • OCT4 • CDX2 • Differentiation • Microarrays

Correspondence: James Adjaye, Ph.D., Max-Planck Institute for Molecular Genetics (Department of Vertebrate Genomics), Ihnestrasse 73, D-14195 Berlin, Germany. Telephone: 0049-30-8413-1216; Fax: 0049-30-8413-1128; e-mail: adjaye{at}molgen.mpg.de

The primary differentiation event during mammalian development occurs at the blastocyst stage and leads to the delineation of the inner cell mass (ICM) and the trophectoderm (TE). We provide the first global mRNA expression data from immunosurgically dissected ICM cells, TE cells, and intact human blastocysts. Using a cDNA microarray composed of 15,529 cDNAs from known and novel genes, we identify marker transcripts specific to the ICM (e.g., OCT4/POU5F1, NANOG, HMGB1, and DPPA5) and TE (e.g., CDX2, ATP1B3, SFN, and IPL), in addition to novel ICM- and TE-specific expressed sequence tags. The expression patterns suggest that the emergence of pluripotent ICM and TE cell lineages from the morula is controlled by metabolic and signaling pathways, which include inter alia, WNT, mitogen-activated protein kinase, transforming growth factor-beta, NOTCH, integrin-mediated cell adhesion, phosphatidylinositol 3-kinase, and apoptosis. These data enhance our understanding of the first step in human cellular differentiation and, hence, the derivation of both embryonic stem cells and trophoblastic stem cells from these lineages.

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