Distinct gene expression signatures in human embryonic stem cells differentiated towards definitive endoderm at single-cell level

Norrman, Karin; Strömbeck, Anna; Semb, Henrik; Ståhlberg, Anders

doi:10.1016/j.ymeth.2012.03.030

Cited by 20 publications

(15 citation statements)

References 58 publications

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“…Specific marker genes that are expressed during embryonic development of definitive endoderm include SRY (sex determining region Y)-box 17 (Sox17) and forkhead box A2 (Foxa2). Expression of these genes specifies foregut endoderm, which subsequently gives rise to pancreatic and hepatic cells [54]. …”

Section: Pluripotent Stem Cells For Disease Modeling and Regenerativementioning

confidence: 99%

Induced Pluripotent Stem Cells as a Source of Hepatocytes

et al. 2014

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During the past decade, a series of discoveries has established the potential of the so called terminally differentiated cells to transition to more primitive progenitor cells. The dramatic demonstration of the ability to reprogram differentiated somatic cells to induced pluripotent stem cells (iPSC) that can then give rise to cells of all three germ layers has opened the possibility of generating virtually any cell type in culture, from any given individual. Taking advantage of these concepts, researchers have generated iPSCs by reprogramming a wide variety of somatic cells. In addition to their practical implications, these studies have provided crucial insights into the mechanism of cell plasticity that underlies the transition from one cell type to another. Using concepts derived from research on embryological development, investigators have differentiated iPSCs to cells resembling hepatocytes in many ways. Such hepatocyte-like cells could be of enormous value in disease modeling, drug discovery and regenerative medicine. However, the currently available methods do not yield cells that fully reproduce the characteristics of adult primary hepatocytes. Thus generating hepatocytes from iPSCs is very much a work in progress. In addition to chronicling these exciting developments, this review will discuss the emergent new approaches to generating iPSCs, improving their differentiation to hepatocyte-like cells and maintaining the hepatocyte-like cells in culture for longer survival and better function.

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Section: Pluripotent Stem Cells For Disease Modeling and Regenerativementioning

confidence: 99%

Induced Pluripotent Stem Cells as a Source of Hepatocytes

et al. 2014

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“…Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) (Thomson et al, 1998) and human induced pluripotent stem cells (hiPSCs) (Takahashi et al, 2007; Yu et al, 2007), have the capacity to differentiate into various cell types, accompanied by dynamic alterations in gene expression patterns (Drukker et al, 2012; Fathi et al, 2011; Norrman et al, 2013; Yang et al, 2013). hESCs/iPSCs maintain their undifferentiated state by expressing pluripotency-associated genes, such as POU5F1 , NANOG and SOX2 .…”

Section: Introductionmentioning

confidence: 99%

Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells

et al. 2016

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Harnessing epigenetic regulation is crucial for the efficient and proper differentiation of pluripotent stem cells (PSCs) into desired cell types. Histone H3 lysine 27 trimethylation (H3K27me3) functions as a barrier against cell differentiation through the suppression of developmental gene expression in PSCs. Here, we have generated human PSC (hPSC) lines in which genome-wide reduction of H3K27me3 can be induced by ectopic expression of the catalytic domain of the histone demethylase JMJD3 (called JMJD3c). We found that transient, forced demethylation of H3K27me3 alone triggers the upregulation of mesoendodermal genes, even when the culture conditions for the hPSCs are not changed. Furthermore, transient and forced expression of JMJD3c followed by the forced expression of lineage-defining transcription factors enabled the hPSCs to activate tissue-specific genes directly. We have also shown that the introduction of JMJD3c facilitates the differentiation of hPSCs into functional hepatic cells and skeletal muscle cells. These results suggest the utility of the direct manipulation of epigenomes for generating desired cell types from hPSCs for cell transplantation therapy and platforms for drug screenings.

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“…The cholangitic transcriptional network has been found to be closely linked in part to factors that are crucial to define further growth of the endoderm into either the pancreatic or hepatic lineage, since the suppression of the marker genes of the definitive endoderm Sox17 and FoxA2 (needed to specify foregut endoderm and subsequent derivation), results in cholangiocyte hyperplasia associated to an excessive expression of IL-6. 48,49 During the hepatoblast stage, T-box transcription factor (Tbx)-3 not only takes part in hepatoblast migration into the septum transversum along with other factors such as prosperorelated homeobox (Prox)-1, but is fundamental too in increasing the expression of HNF 6 and HNF1b and decreasing the level of HNF4a. This is an essential process, as HNF4a together with alpha-fetoprotein (AFP) are key markers of hepatocyte fate commitment; consequently, their expression should be repressed in order to facilitate biliary differentiation.…”

Section: Current and Potential Strategies For Maturation Of Human Ipsmentioning

confidence: 99%

Current strategies to generate mature human induced pluripotent stem cells derived cholangiocytes and future applications

et al. 2017

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ABSTRACT. Stem cell research has significantly evolved over the last few years, allowing the differentiation of pluripotent cells into almost any kind of lineage possible. Studies that focus on the liver have considerably taken a leap into this novel technology, and hepatocyte-like cells are being generated that are close to resembling actual hepatocytes both genotypically and phenotypically. The potential of this extends from disease models to bioengineering, and even also innovative therapies for end-stage liver disease. Nonetheless, too few attention has been given to the non-parenchymal cells which are also fundamental for normal liver function. This includes cholangiocytes, the cells of the biliary epithelium, without whose role in bile modification and metabolism would impair hepatocyte survival. Such can be observed in diseases that target them, so called cholangiopathies, for which there is much yet to study so as to improve therapeutical options. Protocols that describe the induction of human induced pluripotent stem cells into cholangiocytes are scarce, although progress is being achieved in this area as well. In order to give the current view on this emerging research field, and in hopes to motivate further advances, we present here a review on the known differentiation strategies with sight into future applications.

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Distinct gene expression signatures in human embryonic stem cells differentiated towards definitive endoderm at single-cell level

Cited by 20 publications

References 58 publications

Induced Pluripotent Stem Cells as a Source of Hepatocytes

Induced Pluripotent Stem Cells as a Source of Hepatocytes

Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells

Current strategies to generate mature human induced pluripotent stem cells derived cholangiocytes and future applications

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