Expression of FGF19 in human embryonic stem cells

Krejčı́, Pavel; Kunová, Michaela; Kubíková, Iva; Trantı́rek, Lukáš; Kozubı́k, Alois; Dvořák, Petr

doi:10.1002/stem.1493

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…However, endogenous FGF2 levels in supernatants of differentiating cells were medium (d3) to low (d5 to d15). FGF8, FGF17, and FGF19 were detected in medium to high levels in supernatants of hPSCs (Figure ) but only for FGF19 expression in hPSCs has been shown before . The levels of FGF8, FGF17, and FGF19 as well as of the FGF signaling inhibitor TSKU were augmented on d3 of differentiation and declined afterward (Figure ).…”

Section: Resultsmentioning

confidence: 65%

Quantitative Secretomics Reveals Extrinsic Signals Involved in Human Pluripotent Stem Cell Cardiomyogenesis

et al. 2018

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Human pluripotent stem cells can be differentiated in vitro into cardiomyocytes (CMs) but the molecular mechanisms behind this process are still not fully understood. In particular, the identification of morphogens remained elusive because the mass spectrometry-based identification of secreted proteins from cell culture supernatants is impeded by high levels of albumin present in common differentiation media. An albumin-free cardiomyogenic differentiation medium is established in this study and applied for secretomics at seven different time points during in vitro differentiation. By this analysis 4832 proteins are identified with 1802 being significantly altered during differentiation and 431 of these are annotated as secreted. Numerous extrinsic components of Wnt, TGFβ, Activin A, Nodal, BMP, or FGF signaling pathways are quantitatively assessed during differentiation. Notably, the abundance of pathway agonists is generally lower compared to the respective antagonists but their curves of progression over timer were rather similar. It is hypothesized that TGFβ, Activin A, and Nodal signaling are turned down shortly upon the initiation of cardiac differentiation whereas BMP signaling is switched on. Wnt and FGF signaling peaks between d0 and d3 of differentiation, and interestingly, Activin A and TGFβ signaling seem to be reactivated at the cardiac progenitor stages and/or in early CMs.

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Section: Resultsmentioning

confidence: 65%

Quantitative Secretomics Reveals Extrinsic Signals Involved in Human Pluripotent Stem Cell Cardiomyogenesis

et al. 2018

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“…Several bovine ICM‐dominant genes detected in our experiment were found to be overexpressed in mESCs and involve in their self‐renewal and pluripotent maintenance, including ID1 (Romero‐Lanman, Pavlovic, Amlani, Chin, & Benezra, ), OTX2 (Acampora, Di Giovannantonio, & Simeone, ), SMAD6 (Itoh, Watabe, & Miyazono, ), STAT3 , IL6ST (Richards, Tan, Tan, Chan, & Bongso, ) and PRDM14 (Yamaji et al., ). Meanwhile, several other bovine ICM‐dominant genes have also been found to be overexpressed in hESCs and take part in their pluripotent maintenance, including FGF19 (Krejci et al., ), PRDM14 (Chia et al., ), ADD2 (Sato et al., ), FGFR4 (Sato et al., ; Yan et al., ) and JARID2 (Peng et al., ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analyses of inner cell mass and trophectoderm cells isolated by magnetic‐activated cell sorting from bovine blastocysts using single cell RNA‐seq

Zhao

Huang

et al. 2016

Reprod Domestic Animals

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Research on bovine embryonic stem cells (bESCs) has been hampered because bESCs are cultured in conditions that are based on information obtained from culturing mouse and human inner cell mass (ICM) cells. The aim of this study was to compare gene expression in ICM and trophectoderm (TE) cell lineages of bovine embryos and to discuss the findings relative to information available for mice and humans. We separated a high-purity (>90%) ICM and TE from bovine blastocysts by magnetic-activated cell sorting and analysed their transcriptomes by single cell RNA-seq. Differentially expressed genes (DEGs) were assessed using Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases. Finally, qRT-PCR was performed to validate the RNA-seq results. From 207 DEGs identified (adjusted p ≤ .05; fold change ≥2), 159 and 48 had greater expression in the ICM and TE cells respectively. We validated 27 genes using qRT-PCR and found their expression patterns were mostly similar to those of RNA-seq, including 12 novel ICM-dominant (HNF4A, CCL24, FGFR4, IFITM3, PTCHD2, GJB5, FN1, KLK7, PRDM14, GRP, FGF19 and GCM1) and two novel TE-dominant (SLC10A1 and WNT4) genes. Bioinformatics analysis showed that these DEGs are involved in many important pathways, such as MAPK and cancer cell pathways, and these pathways have been shown to play essential roles in mouse and human ESCs in the self-renewal and pluripotent maintenance. As a conclusion, there were sufficient differences to allow us to conclude that the control of pluripotency in bovine ICM cells is species-specific.

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“…In the human fetus, in situ hybridization and RT-PCR analyses reveal FGF19 expression in brain, skin, cartilage, inner retina, small intestine, kidney, as well as placental villi and the umbilical cord (20). FGF19 is also expressed in human embryonic stem cells, and expression levels correlate positively with the undifferentiated state (61). In adulthood, FGF19 expression is detected in biopsies from human ileum, but not in biopsies from human colon (62).…”

Section: Tissue Specificity Of Fgf15/19 Expressionmentioning

confidence: 99%

Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives

Somm

Jornayvaz

2018

Endocrine Reviews

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Discovered 20 years ago, fibroblast growth factor (FGF)19, and its mouse ortholog FGF15, were the first members of a new subfamily of FGFs able to act as hormones. During fetal life, FGF15/19 is involved in organogenesis, affecting the development of the ear, eye, heart, and brain. At adulthood, FGF15/19 is mainly produced by the ileum, acting on the liver to repress hepatic bile acid synthesis and promote postprandial nutrient partitioning. In rodents, pharmacologic doses of FGF19 induce the same antiobesity and antidiabetic actions as FGF21, with these metabolic effects being partly mediated by the brain. However, activation of hepatocyte proliferation by FGF19 has long been a challenge to its therapeutic use. Recently, genetic reengineering of the molecule has resolved this issue. Despite a global overlap in expression pattern and function, murine FGF15 and human FGF19 exhibit several differences in terms of regulation, molecular structure, signaling, and biological properties. As most of the knowledge originates from the use of FGF19 in murine models, differences between mice and humans in the biology of FGF15/19 have to be considered for a successful translation from bench to bedside. This review summarizes the basic knowledge concerning FGF15/19 in mice and humans, with a special focus on regulation of production, morphogenic properties, hepatocyte growth, bile acid homeostasis, as well as actions on glucose, lipid, and energy homeostasis. Moreover, implications and therapeutic perspectives concerning FGF19 in human diseases (including obesity, type 2 diabetes, hepatic steatosis, biliary disorders, and cancer) are also discussed.

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Expression of FGF19 in human embryonic stem cells

Cited by 9 publications

References 10 publications

Quantitative Secretomics Reveals Extrinsic Signals Involved in Human Pluripotent Stem Cell Cardiomyogenesis

Quantitative Secretomics Reveals Extrinsic Signals Involved in Human Pluripotent Stem Cell Cardiomyogenesis

Transcriptome analyses of inner cell mass and trophectoderm cells isolated by magnetic‐activated cell sorting from bovine blastocysts using single cell RNA‐seq

Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives

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