Effect of low dose bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells

The endometrium undergoes cyclic regeneration. This regeneration has been attributed to adult stem progenitor cells and developmental mechanisms [1, 2]. A better understanding of human endometrial development may shed light on the mechanisms involved in endometrial regeneration and on early origins of adult endometrial disease. The lack of human fetal endometrial tissue has impeded research in early human endometrial development. We hypothesized that directed differentiation of human embryonic stem cells (hESC) to human endometrial tissue by neonatal mouse uterine mesenchyme represents a novel system to study early development of human endometrium. Recent studies have shown that the neonatal mouse uterine mesenchyme is extremely inductive and undergoes reciprocal signalling with human endometrial epithelial cells [3]. Our aim is to establish a xenograft tissue recombination protocol based on a model for human prostate tissue differentiation using hESC [4]. Our method involved formation of embryoid body (EB) with GFP labelled hESC (ENVY) [5] for recombination with 2x0.5mm pieces of epithelial-free uterine mesenchyme from postnatal day 1 mice. Upon fusion in culture, the recombinant tissue is grafted under the kidney capsule of NOD/SCID mice for 4-12 weeks and monitored by in-vivo imaging. Immunohistochemical analysis of recombinant grafts 4 weeks post transplantation (n=4) revealed immature CK8+CK18+Hoxa10+ human epithelial cells surrounded by mouse mesenchymal cells suggesting differentiation of hESC to epithelial cells possibly of endometrial lineage. The ER+PR+SMA+Hoxa10+ mouse mesenchymal cells surrounding human glands differentiated into SMA+ cells possibly via reciprocal signalling from human epithelial cells. At 8 weeks, we found several CK18+/Hoxa10+ human glands co-expressing CA125. These glands are supported by Hoxa10+ human stromal cells. Further experiments are underway to induce the expression of ER and PR in Hoxa10+ epithelial cells which will be crucial in revealing their endometrial lineage.

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Differentiation Of Human Embryonic Stem Cells Towards Functional Bronchial Epithelial Cells

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1234 ◽

2011 ◽

Author(s):

Katerina Varanou ◽

Carol E. Jones ◽

Clive P. Page

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Epithelial Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Bronchial Epithelial Cells ◽

Bronchial Epithelial

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Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation

International Journal of Molecular Sciences ◽

10.3390/ijms21239052 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9052

Author(s):

Indrek Teino ◽

Antti Matvere ◽

Martin Pook ◽

Inge Varik ◽

Laura Pajusaar ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Target Genes ◽

Expression Patterns ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Cell Types ◽

Early Differentiation

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types.

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