The human amniotic epithelium confers a bias to differentiate toward the neuroectoderm lineage in human embryonic stem cells
- Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico
- Universidad Nacional Autónoma de México, Mexico
- Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Mexico
Abstract
Human embryonic stem cells (hESC) derive from the epiblast and have pluripotent potential. To maintain the conventional conditions of the pluripotent potential in an undifferentiated state, inactivated mouse embryonic fibroblast (iMEF) is used as a feeder layer. However, it has been suggested that hESC under this conventional condition (hESC-iMEF) is an artifact that does not correspond to the in vitro counterpart of the human epiblast. Our previous studies demonstrated the use of an alternative feeder layer of human amniotic epithelial cells (hAEC) to derive and maintain hESC. We wondered if the hESC-hAEC culture could represent a different pluripotent stage than that of naïve or primed conventional conditions, simulating the stage in which the amniotic epithelium derives from the epiblast during peri-implantation. Like the conventional primed hESC-iMEF, hESC-hAEC has the same levels of expression as the 'pluripotency core'; and does not express markers of naïve pluripotency. However, it presents a downregulation of HOX genes and genes associated with the endoderm and mesoderm and it exhibits an increase in the expression of ectoderm lineage genes, specifically in the anterior neuroectoderm. Transcriptome analysis showed in hESC-hAEC an upregulated signature of genes coding for transcription factors involved in neural induction and forebrain development, and the ability to differentiate into a neural lineage was superior in comparison with conventional hESC-iMEF. We propose that the interaction of hESC with hAEC confers hESC a biased potential that resembles the anteriorized epiblast, which is predisposed to form the neural ectoderm.
Data availability
RNA-seq data from Amiqui-1 are available at the ArrayExpress database (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-10347/) under accession number E-MTAB-10347. Source code for the following analyses is available as indicated: BioJupies, https://github.com/MaayanLab/biojupies.
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The amniotic epithelium triggers an alternative state of human pluripotencyArrayExpress database, E-MTAB-10347.
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Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like nicheEuropean Nucleotide Archive, PRJNA352339.
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Profiling human naive and primed pluripotent statesEuropean Nucleotide Archive,PRJNA360413.
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Formative transition of human naïve pluripotent stem cellsEuropean Nucleotide Archive, PRJNA507424.
Article and author information
Author details
Funding
Instituto Nacional de Perinatología (21041 and 21081)
- Nestor F Diaz
Consejo Nacional de Ciencia y Tecnología (130627,252756 and A1-S-8450)
- Nestor F Diaz
Consejo Nacional de Ciencia y Tecnología (300638,271307)
- Nestor Emmanuel Diaz-Martinez
FONDECIJAL (8084-2019)
- Nestor Emmanuel Diaz-Martinez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joshua M Brickman, University of Copenhagen, Denmark
Publication history
- Received: March 2, 2021
- Accepted: July 8, 2022
- Accepted Manuscript published: July 11, 2022 (version 1)
- Version of Record published: July 25, 2022 (version 2)
Copyright
© 2022, Ávila-González et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The human amniotic epithelium confers a bias to differentiate toward the neuroectoderm lineage in human embryonic stem cells
eLife 11:e68035.
https://doi.org/10.7554/eLife.68035
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