title: KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas.
abstract: Differentiated derivatives of human pluripotent stem cells in culture are generally phenotypically immature compared to their adult counterparts. Their identity is often difficult to determine with certainty because little is known about their human fetal equivalents in vivo. Cellular identity and signaling pathways directing differentiation are usually determined by extrapolating information from either human adult tissue or model organisms, assuming conservation with humans. To resolve this, we generated a collection of human fetal transcriptional profiles at different developmental stages. Moreover, we developed an algorithm, KeyGenes, which uses this dataset to quantify the extent to which next-generation sequencing or microarray data resemble specific cell or tissue types in the human fetus. Using KeyGenes combined with the human fetal atlas, we identified multiple cell and tissue samples unambiguously on a limited set of features. We thus provide a flexible and expandable platform to monitor and evaluate the efficiency of differentiation in vitro.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Roost
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: van Iperen
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Ariyurek
authors.affiliation: Leiden Genome Technology Center, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Buermans
authors.affiliation: Sequence Analysis Support Core, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Wibowo
authors.initials: W
authors.lastname: Arindrarto
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Harsha D
authors.initials: HD
authors.lastname: Devalla
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
authors.forename: Françoise
authors.initials: F
authors.lastname: Carlotti
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Eelco J P
authors.initials: EJ
authors.lastname: de Koning
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
authors.forename: Erik W
authors.initials: EW
authors.lastname: van Zwet
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Geert Grooteplein 21, 6525 EZ Nijmegen, the Netherlands.
authors.forename: Jelle J
authors.initials: JJ
authors.lastname: Goeman
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands; Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. Electronic address: lopes@lumc.nl.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chuva de Sousa Lopes
mesh_terms: D000465:Algorithms; D002454:Cell Differentiation; D016208:Databases, Factual; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics / Q000378:metabolism; D011262:Pregnancy Trimester, Second / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D059467:Transcriptome