The human amniotic epithelium confers a bias to differentiate toward the neuroectoderm lineage in human embryonic stem cells

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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.

The following data sets were generated

(2022) The amniotic epithelium triggers an alternative state of human pluripotency
ArrayExpress database, E-MTAB-10347.

https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-10347/

The following previously published data sets were used

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(2014) RNA-Seq of 3iL human embryonic stem cells with an induced expression profile that more closely resembles native pluripotent cells and uninduced controls
ArrayExpress, E-MTAB-2031.

https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2031/
(2017) RNA-seq of chemically reset human naive pluripotent stem cells
ArrayExpress, E-MTAB-5674.

https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5674/
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https://www.ebi.ac.uk/ena/browser/view/PRJNA507424
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ArrayExpress, E-MTAB-7253.

https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7253/
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(2020) Derivation of formative like pluripotent stem cells from mamalian embryos (RNA-Seq)
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135989

Article and author information

Author details

Daniela Ávila-González

Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico

For correspondence
siriusyami@gmail.com

Competing interests
The authors declare that no competing interests exist.
Wendy Portillo

Behavioral and Cognitive Neurobiology, Universidad Nacional Autónoma de México, Querétaro, Mexico

Competing interests
The authors declare that no competing interests exist.
Carla P Barragán-Álvarez

Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico

Competing interests
The authors declare that no competing interests exist.
Georgina Hernandez-Montes

Red Apoyo a la Investigacion UNAM, Universidad Nacional Autónoma de México, Mexico City, Mexico

Competing interests
The authors declare that no competing interests exist.
Eliezer Flores-Garza

Departamento de Biología Molecular y Biotecnología, Universidad Nacional Autónoma de México, Mexico City, Mexico

Competing interests
The authors declare that no competing interests exist.
Anayansi Molina-Hernández

Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico

Competing interests
The authors declare that no competing interests exist.
Nestor Emmanuel Diaz-Martinez

Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico

Competing interests
The authors declare that no competing interests exist.
Nestor F Diaz

Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico

For correspondence
nfdiaz00@yahoo.com.mx

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2436-9374

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.

Copyright

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.