Human Embryo-Like Model Derived from Stem Cells Opens New Paths for Research – Neuroscience News

Summary: The researchers developed a model derived from human embryonic stem cells in the laboratory. This innovative model, created from pluripotent stem cells, allows for the experimental modeling of embryonic development during the second week of pregnancy, a critical period often associated with pregnancy termination.

The research aims to improve our understanding of genetic diseases, early pregnancy loss and the origins of specialized cells and organs. This new advance could reduce reliance on donated human embryos in research.

Main aspects:

  1. Cambridge scientists have created a model of the human embryo in the laboratory using reprogrammed human stem cells.
  2. The model allows for experimental modeling of embryonic development during the second week of pregnancy, a time when many pregnancies fail.
  3. This breakthrough could improve our understanding of genetic diseases, early pregnancy loss, and the origins of the development of specialized cells and organs, and could reduce the need for donated human embryos in research.

Source: University of Cambridge

Cambridge scientists have created a stem cell-derived model of the human embryo in the lab by reprogramming human stem cells. The breakthrough could help research into genetic disorders and understand why and how pregnancies fail.

Published today in the magazineNatureThis embryo model is an organized three-dimensional structure derived from pluripotent stem cells that replicate certain developmental processes that occur in early human embryos.

The use of such models allows for the experimental modeling of embryonic development during the second week of pregnancy. They can help researchers gain basic knowledge about the developmental origins of specialized cells and organs such as sperm and eggs, and facilitate understanding of early abortion.

This shows the cells.
Many pregnancies fail when these three types of cells orchestrate implantation in the uterus and begin exchanging mechanical and chemical signals that tell the embryo how to develop properly. Credit: Neuroscience News

Our human embryo-like model, created entirely from human stem cells, gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo in the mother’s womb, said Professor Magdalena Zernicka-Goetz in the Department of Physiology, Development and Neuroscience at the University of Cambridge, who led the work.

He added: This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will allow us to test the function of specific factors, which is difficult to do in the natural embryo.

In natural human development, the second week of development is an important time when the embryo implants itself in the uterus. This is when many pregnancies are lost.

The new advance allows scientists to peer into the mysterious black box period of human development that usually follows the implantation of the embryo into the uterus to observe processes never directly observed before.

Understanding these early developmental processes has the potential to reveal some of the causes of human birth defects and disease, and to develop tests for these in pregnant women.

Until now, the processes could only be observed in animal models, using cells from zebrafish and mice, for example.

Legal restrictions in the UK currently prevent the cultivation of natural human embryos in the laboratory beyond day 14 of development: this time limit has been set to correspond to the stage at which the embryo can no longer form a twin.

Until now, scientists have only been able to study this period of human development using donated human embryos. This advance could reduce the need for donated human embryos in research.

Zernicka-Goetz says that while these models can mimic aspects of human embryonic development, they cannot and will not develop into the equivalent of postnatal humans.

For the past decade, Zernicka-Goetz’s group in Cambridge has been studying the early stages of pregnancy, to understand why some pregnancies fail and others are successful.

In 2021 and then 2022 his team announced Development cell, Nature AND Cellular stem cell magazines that had finally created model embryos from mouse stem cells that can develop to form a brain-like structure, a beating heart, and the foundation for all other organs in the body.

The new human stem cell-derived models do not have a brain or a beating heart, but include cells that typically would go on to form the embryo, placenta and yolk sac, and will develop to form germ cell precursors (which will form sperm and eggs).

Many pregnancies fail when these three types of cells orchestrate implantation in the uterus and begin exchanging mechanical and chemical signals that tell the embryo how to develop properly.

There are clear rules governing stem cell-based human embryo models, and all researchers undertaking embryo modeling work must first be approved by ethics committees. Journals require proof of this ethical review before accepting scientific articles for publication. The Zernicka-Goetz laboratory holds these approvals.

It is against the law and FDA regulations to transfer any embryo-like pattern into a woman for reproductive purposes. These are highly manipulated human cells and their attempted reproductive use would be extremely dangerous, said Dr. Insoo Hyun, director of the Center for Life Sciences and Public Learning at Bostons Museum of Science and a fellow at the Harvard Medical Schools Center for Bioethics.

Zernicka-Goetz also holds a position at the California Institute of Technology and is a NOMIS Distinguished Scientist and Scholar Awardee.

Financing: The research was funded by the Wellcome Trust and Open Philanthropy.

About this news about stem cell research and neurodevelopment

Author: Craig Brierley
Source: University of Cambridge
Contact: Craig Brierley – University of Cambridge
Image: The image is credited to Neuroscience News

Original research: Access closed.
“A model of the post-implantation human embryo derived from pluripotent stem cells” by Magdalena Zernicka-Goetz et al. Nature


Abstract

A model of the post-implantation human embryo derived from pluripotent stem cells

The human embryo undergoes morphogenetic transformations after implantation in the uterus, however our knowledge of this crucial stage is limited by the impossibility of observing the embryolive. Stem cell-derived models of the embryo are important tools for interrogating developmental events and tissue-tissue crosstalk during these stages.

Here, we establish a model of the human post-implantation embryo, a human embryo, composed of embryonic and extraembryonic tissues.

We combine two types of extraembryonic cells generated by transcription factor overexpression with wild-type embryonic stem cells and promote their self-organization into structures that mimic different aspects of the post-implantation human embryo. These self-organized aggregates contain an epiblast-like pluripotent domain surrounded by extraembryonic tissues.

Our functional studies demonstrate that the epiblast-like domain robustly differentiates from amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP signals. Furthermore, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells.

Modulation of subpopulations in the hypoblast-like compartment demonstrated that extraembryonic cells affect the differentiation of the epiblast-like domain, highlighting functional tissue-tissue crosstalk.

In conclusion, we present a modular, tractable and integrated model of the human embryo that will allow us to probe key questions of post-implantation human development, a critical window when significant numbers of pregnancies fail.

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Image Source : neurosciencenews.com

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