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Single-cell RNA-seq reveals TCF7 as a novel regulator of human induced pluripotent stem cells differentiation to definitive endoderm

ABSTRACT: Endodermal cells differentiated from human induced pluripotent stem cells can produce multiple functional epithelial cells of vital organs and tissues that can be used for disease modeling as well as cell therapy. However, the detailed molecular mechanism of how hiPSCs differentiate towards definitive endoderm is not fully understood. By analyzing single-cell RNA sequencing data of definitive endoderm differentiation from human embryonic stem cells, transcription factor 7 (TCF7) was identified as a gene that transiently increases then decreases during differentiation of definitive endoderm.

ORGANISM(S): Homo sapiens

PROVIDER: GSE280986 | GEO | 2025/04/01

REPOSITORIES: GEO

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Mouse embryonic and induced pluripotent stem cells can form definitive endoderm despite differences in imprinted genes

Project description:The directed differentiation of induced pluripotent stem (iPS) and embryonic stem (ES) cells into definitive endoderm (DE) would allow the derivation of otherwise inaccessible progenitors for endodermal tissues. However, a global comparison of the relative equivalency of DE derived from iPS and ES populations has not been performed. Recent reports of molecular differences between iPS and ES cells have raised uncertainty as to whether iPS cells could generate autologous endodermal lineages in vitro. Here, we have shown that both mouse iPS and parental ES cells exhibited highly similar in vitro capacity to undergo directed differentiation into DE progenitors. With few exceptions, both cell types displayed similar surges in gene expression of specific master transcriptional regulators and global transcriptomes that define the developmental milestones of DE differentiation. Microarray analysis showed considerable overlap between the genetic programs of DE derived from ES/iPS cells in vitro and authentic DE from mouse embryos in vivo. Intriguingly, iPS cells exhibited aberrant silencing of imprinted genes known to participate in endoderm differentiation, yet retained a robust ability to differentiate into DE. Our results show that, despite some molecular differences, iPS cells can be efficiently differentiated into DE precursors, reinforcing their potential for development of cell-based therapies for diseased endodermal-derived tissues. Comparison of mouse ES cells, mouse iPS cells, and E8.25 Mouse embryos; in the undifferentiated state and definitive endoderm differentiated state. ckit+/Sox2dim =definitive endoderm (day 5 of differentiation in vitro); Sox2bright =undifferentiated ES or iPS cells (day 0 of differentiation); ENDM1+/Epcam+/SSlo=foregut endoderm sorted from mouse E8.25 embryos; Epcam+/ENDM1 negative =sorted comparison population from mouse E8.25 embryos.

2011-03-31 | E-GEOD-27087 | biostudies-arrayexpress

Pluripotency Factors Regulate Definitive Endoderm Specification through Eomesodermin

Project description:Understanding the molecular mechanisms controlling early cell fate decisions in mammals is a major objective towards the development of robust methods for the differentiation of human pluripotent stem cells into clinically relevant cell types. Here, we used human embryonic stem cells (hESCs) to study specification of definitive endoderm in vitro. Using a combination of whole genome expression and ChIP-seq analyses, we established a hierarchy of transcription factors regulating endoderm specification. Importantly, pluripotency factors, namely NANOG, OCT4 and SOX2 have an essential function in this network by actively directing differentiation. Indeed, these transcription factors control the expression of EOMES, which marks the onset of endoderm specification. In turn, EOMES interacts with SMAD2/3 to initiate the transcriptional network governing endoderm formation. Together, these results provide for the first time a comprehensive molecular model connecting the transition from pluripotency to endoderm specification during mammalian development. ChIP-Seq of Eomesodermin binding in human embyonic stem cells, differentiated towards an endodermal fate for 48h in chemically-defined culture media. Includes an input DNA control. Supplementary file GSE26097_README.txt contains descriptions of the raw data files and processed data files.

2011-01-25 | E-GEOD-26097 | biostudies-arrayexpress

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Project description:Using a well-established human definitive endoderm differentiation system, we can analyze the gene expression dynamic of human embryonic stem cells (hESCs) during endoderm differentiation. Samples from hESCs, D2 cells and definitive endoderm cells (DE) were collected for deep sequencing with two replicates for each sample. Differentially expressed genes analysis showed that endodermal genes were induced during endoderm differentiation.

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Saracatinib Promotes Definitive Endoderm Differentiation by Inhibition of FAK-YAP Signaling Axis

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Generation of pancreatic β cells from CD177+ anterior definitive endoderm

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A distinct microRNA signature for definitive endoderm derived from human embryonic stem cells

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2010-07-30 | E-GEOD-16690 | biostudies-arrayexpress

Wild-type and TP53 genetic knockout BOBSC hiPS cells were maintained in the undifferentiated state or differentiated to definitive endoderm over 72 hours, with or without 5 ppm MMS treatment at 24 hours.

Project description:The ability of human induced pluripotent stem cells (hiPSCs) to differentiate in vitro to each of the three germ layer lineages has made them an important developmental model and tool for tissue engineering. Here we explore the impact of inducing DNA damage at different points during differentiation. We show that, during a critical window in this program, DNA damage diverts cells from an endodermal to mesodermal fate without significant upregulation of an apoptotic program. This change in transcriptional program is driven by p53: cells lacking p53 continue to differentiate towards endoderm with high efficiency despite significant genomic damage and G2/M cell cycle arrest. Thus, DNA damage-induced upregulation of p53 decreases the efficiency of hiPSC differentiation to definitive endoderm by diverting cells towards a mesodermal fate.

2020-07-27 | GSE146225 | GEO

Dynamic developmental signaling logic underlying lineage bifurcations during human endoderm induction and patterning from pluripotent stem cells [Expression data set]

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Mouse embryonic and induced pluripotent stem cells can form definitive endoderm despite differences in imprinted genes

2011-03-31 | GSE27087 | GEO

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