An in vitro model of human yolk sac and epiblast crosstalk
type: CreativeWork
description: Embryogenesis entails complex signalling interactions between embryonic and extraembryonic lineages. Improved embryo culture techniques have recently allowed human embryos to be cultured in vitro past the point at which they would implant in vivo, until the internationally accepted culture limit of 14 days. Nonetheless, the reliance on surplus in vitro fertilised (IVF) embryos, along with the ethical and legal considerations associated with genetic manipulation of human embryos, present barriers to the study of postimplantation human development. However, human stem cell-based embryo models offer a system that is amenable to genetic and molecular manipulation. Within mouse development, the anterior visceral endoderm (AVE), formed from the extraembryonic endoderm, plays a crucial role in restricting primitive streak formation to the posterior epiblast, thereby establishing the anterior-posterior axis of the mouse embryo. Recent studies of human embryos cultured to postimplantation stages have alluded to the presence of a human equivalent of the mouse AVE in the anterior hypoblast, the hypoblast being the portion of the human yolk sac that lies adjacent to the epiblast. However, the functional role of such a structure within the context of human development is yet to be understood. In vitro stem cell modelling of the human yolk sac- epiblast interaction offers a system through which the role of the yolk sac in postimplantation epiblast morphogenesis can be interrogated. Consequently, the aim of this study was to derive yolk sac-like cells (YSLCs) that could be used to model human epiblast-yolk sac crosstalk in vitro. Following a screen of developmentally relevant signalling pathway activators, this project identified that the coactivation of NODAL, WNT and JAK/STAT signalling via ACTIVIN-A, CHIRON, and leukaemia inhibitory factor (LIF) (ACL) induced an endodermal fate in human pluripotent stem cells (hPSCs). Functional and transcriptional analysis of ACL-treated cell …
abstract: Embryogenesis entails complex signalling interactions between embryonic and extraembryonic lineages. Improved embryo culture techniques have recently allowed human embryos to be cultured in vitro past the point at which they would implant in vivo, until the internationally accepted culture limit of 14 days. Nonetheless, the reliance on surplus in vitro fertilised (IVF) embryos, along with the ethical and legal considerations associated with genetic manipulation of human embryos, present barriers to the study of postimplantation human development. However, human stem cell-based embryo models offer a system that is amenable to genetic and molecular manipulation. Within mouse development, the anterior visceral endoderm (AVE), formed from the extraembryonic endoderm, plays a crucial role in restricting primitive streak formation to the posterior epiblast, thereby establishing the anterior-posterior axis of the mouse embryo. Recent studies of human embryos cultured to postimplantation stages have alluded to the presence of a human equivalent of the mouse AVE in the anterior hypoblast, the hypoblast being the portion of the human yolk sac that lies adjacent to the epiblast. However, the functional role of such a structure within the context of human development is yet to be understood. In vitro stem cell modelling of the human yolk sac- epiblast interaction offers a system through which the role of the yolk sac in postimplantation epiblast morphogenesis can be interrogated. Consequently, the aim of this study was to derive yolk sac-like cells (YSLCs) that could be used to model human epiblast-yolk sac crosstalk in vitro. Following a screen of developmentally relevant signalling pathway activators, this project identified that the coactivation of NODAL, WNT and JAK/STAT signalling via ACTIVIN-A, CHIRON, and leukaemia inhibitory factor (LIF) (ACL) induced an endodermal fate in human pluripotent stem cells (hPSCs). Functional and transcriptional analysis of ACL-treated cell …
author: Mackinlay, Kirsty
language: eng
keywords: stem cell, embryology, hESCs, hypoblast, human embryo, epiblast, trophoblast, human development
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2022-02-28
date modified: 2026-07-22T22:24:23Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.87212