Martinez-Barbera, J;
(2019)
Genetic Deletion of Hesx1 Promotes Exit from the Pluripotent State and Impairs Developmental Diapause.
Stem Cell Reports
, 13
(6)
pp. 970-979.
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Abstract
The role of the homeobox transcriptional repressor HESX1 in embryonic stem cells (ESCs) remains mostly unknown. Here, we show that Hesx1 is expressed in the preimplantation mouse embryo, where it is required during developmental diapause. Absence of Hesx1 leads to reduced expression of epiblast and primitive endoderm determinants and failure of diapaused embryos to resume embryonic development after implantation. Genetic deletion of Hesx1 impairs self-renewal and promotes differentiation toward epiblast by reducing the expression of pluripotency factors and decreasing the activity of LIF/STAT3 signaling. We reveal that Hesx1-deficient ESCs show elevated ERK pathway activation, resulting in accelerated differentiation toward primitive endoderm, which can be prevented by overexpression of Hesx1. Together, our data provide evidence for a novel role of Hesx1 in the control of self-renewal and maintenance of the undifferentiated state in ESCs and mouse embryos.
| Type: | Article |
|---|---|
| Title: | Genetic Deletion of Hesx1 Promotes Exit from the Pluripotent State and Impairs Developmental Diapause |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | https://doi.org/10.1016/j.stemcr.2019.10.014 |
| Language: | English |
| Additional information: | © 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Hesx1, pluripotency, diapause, embryonic stem cells, mouse development, LIF/STAT3 signaling, ERK pathway |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10085324 |
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