Please use this identifier to cite or link to this item: doi:10.22028/D291-29529
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Title: Assessment of stem cell differentiation based on genome-wide expression profiles
Author(s): Godoy, Patricio
Schmidt-Heck, Wolfgang
Hellwig, Birte
Nell, Patrick
Feuerborn, David
Rahnenführer, Jörg
Kattler, Kathrin
Walter, Jörn Erik
Blüthgen, Nils
Hengstler, Jan G.
Language: English
Title: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Volume: 373
Issue: 1750
Publisher/Platform: Royal Society of London
Year of Publication: 2018
Publikation type: Journal Article
Abstract: In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue. It consists of a principal component analysis to represent global expression changes and to identify possible problems of the dataset that require special attention, such as: batch effects; clustering techniques to identify gene groups with similar features; over-representation analysis to characterize biological motifs and transcriptional control factors of the identified gene clusters; and metagenes as well as gene regulatory networks for quantitative cell-type assessment and identification of influential transcription factors. Possibilities and limitations of the analysis pipeline are illustrated using the example of human embryonic stem cell and human induced pluripotent cells to generate 'hepatocyte-like cells'. The pipeline quantifies the degree of incomplete differentiation as well as remaining stemness and identifies unwanted features, such as colon- and fibroblast-associated gene clusters that are absent in real hepatocytes but typically induced by currently available differentiation protocols. Finally, transcription factors responsible for incomplete and unwanted differentiation are identified. The proposed method is widely applicable and allows an unbiased and quantitative assessment of stem cell-derived cells.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.
DOI of the first publication: 10.1098/rstb.2017.0221
Link to this record: hdl:20.500.11880/27917
ISSN: 0962-8436
Date of registration: 26-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Jörn Walter
Collections:Die Universitätsbibliographie

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