title: Gene expression signatures defining fundamental biological processes in pluripotent, early, and late differentiated embryonic stem cells.
abstract: Investigating the molecular mechanisms controlling the in vivo developmental program postembryogenesis is challenging and time consuming. However, the developmental program can be partly recapitulated in vitro by the use of cultured embryonic stem cells (ESCs). Similar to the totipotent cells of the inner cell mass, gene expression and morphological changes in cultured ESCs occur hierarchically during their differentiation, with epiblast cells developing first, followed by germ layers and finally somatic cells. Combination of high throughput -omics technologies with murine ESCs offers an alternative approach for studying developmental processes toward organ-specific cell phenotypes. We have made an attempt to understand differentiation networks controlling embryogenesis in vivo using a time kinetic, by identifying molecules defining fundamental biological processes in the pluripotent state as well as in early and the late differentiation stages of ESCs. Our microarray data of the differentiation of the ESCs clearly demonstrate that the most critical early differentiation processes occur at days 2 and 3 of differentiation. Besides monitoring well-annotated markers pertinent to both self-renewal and potency (capacity to differentiate to different cell lineage), we have identified candidate molecules for relevant signaling pathways. These molecules can be further investigated in gain and loss-of-function studies to elucidate their role for pluripotency and differentiation. As an example, siRNA knockdown of MageB16, a gene highly expressed in the pluripotent state, has proven its influence in inducing differentiation when its function is repressed.
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Cologne, Germany.
authors.forename: John Antonydas
authors.initials: JA
authors.lastname: Gaspar
authors.forename: Michael Xavier
authors.initials: MX
authors.lastname: Doss
authors.forename: Johannes
authors.initials: J
authors.lastname: Winkler
authors.forename: Vilas
authors.initials: V
authors.lastname: Wagh
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Raivo
authors.initials: R
authors.lastname: Kolde
authors.forename: Jaak
authors.initials: J
authors.lastname: Vilo
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D025341:Principal Component Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D034741:RNA, Small Interfering