2022
Kotasová, Hana; Capandová, Michaela; Pelková, Vendula; Dumková, Jana; Koledová, Zuzana; Remšík, Ján; Souček, Karel; Garlíková, Zuzana; Sedláková, Veronika; Rabata, Anas; Vaňhara, Petr; Moráň, Lukáš; Pečinka, Lukáš; Porokh, Volodymyr; Kučírek, Martin; Streit, Libor; Havel, Josef; Hampl, Aleš
Expandable Lung Epithelium Differentiated from Human Embryonic Stem Cells. Journal Article
In: Tissue engineering and regenerative medicine, vol. 19, no. 5, pp. 1033–1050, 2022, ISSN: 2212-5469 1738-2696, (Place: Korea (South)).
Abstract | Links | BibTeX | Tags: *Human Embryonic Stem Cells, Cell Differentiation, Differentiation, Epithelium, Foregut endoderm, hESC, Humans, Lung, Lung/metabolism, Surface-Active Agents/metabolism
@article{kotasova_expandable_2022,
title = {Expandable Lung Epithelium Differentiated from Human Embryonic Stem Cells.},
author = {Hana Kotasová and Michaela Capandová and Vendula Pelková and Jana Dumková and Zuzana Koledová and Ján Remšík and Karel Souček and Zuzana Garlíková and Veronika Sedláková and Anas Rabata and Petr Vaňhara and Lukáš Moráň and Lukáš Pečinka and Volodymyr Porokh and Martin Kučírek and Libor Streit and Josef Havel and Aleš Hampl},
doi = {10.1007/s13770-022-00458-0},
issn = {2212-5469 1738-2696},
year = {2022},
date = {2022-10-01},
journal = {Tissue engineering and regenerative medicine},
volume = {19},
number = {5},
pages = {1033–1050},
abstract = {BACKGROUND: The progenitors to lung airway epithelium that are capable of long-term propagation may represent an attractive source of cells for cell-based therapies, disease modeling, toxicity testing, and others. Principally, there are two main options for obtaining lung epithelial progenitors: (i) direct isolation of endogenous progenitors from human lungs and (ii) in vitro differentiation from some other cell type. The prime candidates for the second approach are pluripotent stem cells, which may provide autologous and/or allogeneic cell resource in clinically relevant quality and quantity. METHODS: By exploiting the differentiation potential of human embryonic stem cells (hESC), here we derived expandable lung epithelium (ELEP) and established culture conditions for their long-term propagation (more than 6 months) in a monolayer culture without a need of 3D culture conditions and/or cell sorting steps, which minimizes potential variability of the outcome. RESULTS: These hESC-derived ELEP express NK2 Homeobox 1 (NKX2.1), a marker of early lung epithelial lineage, display properties of cells in early stages of surfactant production and are able to differentiate to cells exhibitting molecular and morphological characteristics of both respiratory epithelium of airway and alveolar regions. CONCLUSION: Expandable lung epithelium thus offer a stable, convenient, easily scalable and high-yielding cell source for applications in biomedicine.},
note = {Place: Korea (South)},
keywords = {*Human Embryonic Stem Cells, Cell Differentiation, Differentiation, Epithelium, Foregut endoderm, hESC, Humans, Lung, Lung/metabolism, Surface-Active Agents/metabolism},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The progenitors to lung airway epithelium that are capable of long-term propagation may represent an attractive source of cells for cell-based therapies, disease modeling, toxicity testing, and others. Principally, there are two main options for obtaining lung epithelial progenitors: (i) direct isolation of endogenous progenitors from human lungs and (ii) in vitro differentiation from some other cell type. The prime candidates for the second approach are pluripotent stem cells, which may provide autologous and/or allogeneic cell resource in clinically relevant quality and quantity. METHODS: By exploiting the differentiation potential of human embryonic stem cells (hESC), here we derived expandable lung epithelium (ELEP) and established culture conditions for their long-term propagation (more than 6 months) in a monolayer culture without a need of 3D culture conditions and/or cell sorting steps, which minimizes potential variability of the outcome. RESULTS: These hESC-derived ELEP express NK2 Homeobox 1 (NKX2.1), a marker of early lung epithelial lineage, display properties of cells in early stages of surfactant production and are able to differentiate to cells exhibitting molecular and morphological characteristics of both respiratory epithelium of airway and alveolar regions. CONCLUSION: Expandable lung epithelium thus offer a stable, convenient, easily scalable and high-yielding cell source for applications in biomedicine.
2011
Procházková, Jirina; Kabátková, Markéta; Bryja, Vítezslav; Umannová, Lenka; Bernatík, Ondrej; Kozubík, Alois; Machala, Miroslav; Vondrácek, Jan
In: Toxicological sciences : an official journal of the Society of Toxicology, vol. 122, no. 2, pp. 349–360, 2011, ISSN: 1096-0929, (Place: United States).
Abstract | Links | BibTeX | Tags: Animals, Aryl Hydrocarbon Hydroxylases/genetics/metabolism, Aryl Hydrocarbon/genetics/*metabolism, beta Catenin/genetics/*metabolism, Cadherins/genetics, Cell Adhesion, Cell Differentiation, Cell Line, Cytochrome P-450 CYP1A1/genetics/metabolism, Cytochrome P-450 CYP1B1, Down-Regulation/drug effects, Hepatocytes/drug effects, Inbred F344, Liver/*drug effects, Polychlorinated Dibenzodioxins/toxicity, Rats, Receptors, Wnt Proteins/genetics/*metabolism, Wnt Signaling Pathway
@article{prochazkova_interplay_2011,
title = {The interplay of the aryl hydrocarbon receptor and β-catenin alters both AhR-dependent transcription and Wnt/β-catenin signaling in liver progenitors.},
author = {Jirina Procházková and Markéta Kabátková and Vítezslav Bryja and Lenka Umannová and Ondrej Bernatík and Alois Kozubík and Miroslav Machala and Jan Vondrácek},
doi = {10.1093/toxsci/kfr129},
issn = {1096-0929},
year = {2011},
date = {2011-08-01},
journal = {Toxicological sciences : an official journal of the Society of Toxicology},
volume = {122},
number = {2},
pages = {349–360},
abstract = {β-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/β-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/β-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/β-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active β-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/β-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors. The downregulation of β-catenin was also related to a reduced cell adhesion, disruption of E-cadherin-mediated cell-cell junctions and an increased G1-S transition in liver progenitor cell line. In conclusion, although β-catenin augmented the expression of selected AhR target genes, the persistent AhR activation may lead to downregulation of Wnt/β-catenin signaling, thus altering differentiation and/or proliferative status of liver progenitor cells.},
note = {Place: United States},
keywords = {Animals, Aryl Hydrocarbon Hydroxylases/genetics/metabolism, Aryl Hydrocarbon/genetics/*metabolism, beta Catenin/genetics/*metabolism, Cadherins/genetics, Cell Adhesion, Cell Differentiation, Cell Line, Cytochrome P-450 CYP1A1/genetics/metabolism, Cytochrome P-450 CYP1B1, Down-Regulation/drug effects, Hepatocytes/drug effects, Inbred F344, Liver/*drug effects, Polychlorinated Dibenzodioxins/toxicity, Rats, Receptors, Wnt Proteins/genetics/*metabolism, Wnt Signaling Pathway},
pubstate = {published},
tppubtype = {article}
}
β-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/β-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/β-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/β-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active β-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/β-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors. The downregulation of β-catenin was also related to a reduced cell adhesion, disruption of E-cadherin-mediated cell-cell junctions and an increased G1-S transition in liver progenitor cell line. In conclusion, although β-catenin augmented the expression of selected AhR target genes, the persistent AhR activation may lead to downregulation of Wnt/β-catenin signaling, thus altering differentiation and/or proliferative status of liver progenitor cells.
2006
Stika, Jirí; Vondrácek, Jan; Hofmanová, Jirina; Simek, Vladimír; Kozubík, Alois
MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis. Journal Article
In: Cancer letters, vol. 237, no. 2, pp. 263–271, 2006, ISSN: 0304-3835, (Place: Ireland).
Abstract | Links | BibTeX | Tags: *Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism
@article{stika_mk-886_2006,
title = {MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.},
author = {Jirí Stika and Jan Vondrácek and Jirina Hofmanová and Vladimír Simek and Alois Kozubík},
doi = {10.1016/j.canlet.2005.06.012},
issn = {0304-3835},
year = {2006},
date = {2006-06-01},
journal = {Cancer letters},
volume = {237},
number = {2},
pages = {263–271},
abstract = {We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.},
note = {Place: Ireland},
keywords = {*Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism},
pubstate = {published},
tppubtype = {article}
}
We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.
2003
Nemajerová, Alice; Smarda, Jan; Jurdic, Pierre; Kubala, Lukás; Soucek, Karel; Smardová, Jana
Trichostatin A suppresses transformation by the v-myb oncogene in BM2 cells. Journal Article
In: Journal of hematotherapy & stem cell research, vol. 12, no. 2, pp. 225–235, 2003, ISSN: 1525-8165, (Place: United States).
Abstract | Links | BibTeX | Tags: Acetylation, Animals, Cell Cycle, Cell Differentiation, Cell Line, Cell Transformation, Chickens, Chromatin Assembly and Disassembly/physiology, Genes, Histone Deacetylases/drug effects, Histones/metabolism/physiology, Hydroxamic Acids/*pharmacology, Macrophages/cytology, myb/drug effects/*physiology, Transformed, Viral/*drug effects
@article{nemajerova_trichostatin_2003,
title = {Trichostatin A suppresses transformation by the v-myb oncogene in BM2 cells.},
author = {Alice Nemajerová and Jan Smarda and Pierre Jurdic and Lukás Kubala and Karel Soucek and Jana Smardová},
doi = {10.1089/152581603321628368},
issn = {1525-8165},
year = {2003},
date = {2003-04-01},
journal = {Journal of hematotherapy & stem cell research},
volume = {12},
number = {2},
pages = {225–235},
abstract = {BM2 cells are chicken monoblasts transformed by the v-myb oncogene of avian myeloblastosis virus. The constitutively high v-myb expression interferes with the terminal differentiation of BM2 cells, but these cells can be induced to differentiate into macrophage-like cells by phorbol esters. Histone acetylation plays an important role in regulation of transcription and is particularly relevant to the regulation and pathology of hematopoiesis. In the present study, we examined the contribution of elevated histone acetylation to the differentiation of BM2 cells. Inhibition of the activity of endogenous histone deacetylases by trichostatin A (TSA) resulted in histone hyperacetylation causing cell cycle arrest and differentiation of BM2 cells into macrophage polykaryons. TSA did not affect the level of v-Myb protein in BM2 cells, but it downregulated its transcription activation capability. This suggests that chromatin remodeling can be significantly engaged in regulation of proliferation and differentiation of leukemic cells.},
note = {Place: United States},
keywords = {Acetylation, Animals, Cell Cycle, Cell Differentiation, Cell Line, Cell Transformation, Chickens, Chromatin Assembly and Disassembly/physiology, Genes, Histone Deacetylases/drug effects, Histones/metabolism/physiology, Hydroxamic Acids/*pharmacology, Macrophages/cytology, myb/drug effects/*physiology, Transformed, Viral/*drug effects},
pubstate = {published},
tppubtype = {article}
}
BM2 cells are chicken monoblasts transformed by the v-myb oncogene of avian myeloblastosis virus. The constitutively high v-myb expression interferes with the terminal differentiation of BM2 cells, but these cells can be induced to differentiate into macrophage-like cells by phorbol esters. Histone acetylation plays an important role in regulation of transcription and is particularly relevant to the regulation and pathology of hematopoiesis. In the present study, we examined the contribution of elevated histone acetylation to the differentiation of BM2 cells. Inhibition of the activity of endogenous histone deacetylases by trichostatin A (TSA) resulted in histone hyperacetylation causing cell cycle arrest and differentiation of BM2 cells into macrophage polykaryons. TSA did not affect the level of v-Myb protein in BM2 cells, but it downregulated its transcription activation capability. This suggests that chromatin remodeling can be significantly engaged in regulation of proliferation and differentiation of leukemic cells.