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First published online August 4, 2005
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2005-0113v1
23/10/1514    most recent
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Submitted on March 15, 2005
Accepted on June 12, 2005

Original Article

Primary differentiation in the human blastocyst: Comparative molecular portraits of inner cell mass and trophectoderm cells

James Adjaye 1*, John Huntriss 2, Ralf Herwig 1, Alia BenKahla 1, Thore Brink 1, Christoph Wierling 1, Claus Hultschig 1, Detlef Groth 1, Marie-Laure Yaspo 1, Helen Picton 2, Roger Gosden 3, Hans Lehrach 1

1 Max-Planck Institute for Molecular Genetics, Department of Vertebrate Genomics, Berlin, Germany
2 Reproduction and Early Development Research Group, Department of Obstetrics and Gynaecology, University of Leeds, Belmont Grove, Leeds, W.Yorkshire, United Kingdom
3 Center for Reproductive Medicine & Infertility, Weill Medical College, Cornell University, 505 East 70th Street, New York, New York

* To whom correspondence should be addressed. E-mail: adjaye{at}molgen.mpg.de.


  Abstract

The primary differentiation event during mammalian development occurs at the blastocyst stage and leads to the delineation of the inner cell mass and the trophectoderm. We provide the first global mRNA expression data from immunosurgically dissected inner cell mass (ICM) cells, trophectoderm (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 ESTs. The expression patterns suggest that the emergence of pluripotent ICM and TE cell lineages from the morula is controlled by metabolic and signalling pathways which include, inter alia, WNT, MAPK, TGF-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 (ES) cells and trophoblastic stem (TS) cells from these lineages.

Key Words. Preimplantation development, Blastocyst, Inner Cell Mass, Trophectoderm, Pluripotency, Embryonic stem cells, Trophoblastic stem cells, OCT4, CDX2, Differentiation, Microarrays




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