Human embryo-like model created from human stem cells

Date:
June 11, 2020
Source:
University of Cambridge
Summary:
Scientists have developed a new model to study an early stage of
human development, using human embryonic stem cells.



FULL STORY ========================================================================== Scientists from the University of Cambridge, in collaboration with the
Hubrecht Institute in The Netherlands, have developed a new model to
study an early stage of human development, using human embryonic stem
cells. The model resembles some key elements of an embryo at around
18-21 days old and allows the researchers to observe the processes
underlying the formation of the human body plan never directly observed
before. Understanding these processes holds potential to reveal the
causes of human birth defects and diseases, and to develop tests for
these in pregnant women.


==========================================================================
The body plan, or blueprint of an organism, arises through a process
called 'gastrulation'. During gastrulation, three distinct layers
of cells are formed in the embryo that will later give rise to all
the body's major systems: the ectoderm will make the nervous system,
mesoderm the muscles, and endoderm the gut.

Gastrulation is often referred to as the 'black box' period of human development, because legal restrictions prevent the culture of human
embryos in the lab beyond day 14, when the process starts. This limit
was set to fall at the stage where the embryo can no longer form a twin.

Many birth defects originate during this 'black box' period, with causes including alcohol, medications, chemicals and infections. A better understanding of human gastrulation could also shed light on many medical issues including infertility, miscarriage, and genetic disorders.

"Our model produces part of the blueprint of a human," said Professor
Alfonso Martinez-Arias from the University of Cambridge's Department of Genetics, who led the study. "It's exciting to witness the developmental processes that until now have been hidden from view -- and from study." Published today in the journal Nature, the report describes a method
of using human embryonic stem cells to generate a three-dimensional
assembly of cells, called gastruloids, which differentiate into three
layers organised in a manner that resembles the early human body plan.

To make gastruloids in the lab, defined numbers of human embryonic
stem cells were placed in small wells, where they formed tight
aggregates. After treatment with chemical signals, the gastruloids were
seen to lengthen along a head to tail axis, known as the anteroposterior
axis, turning on genes in specific patterns along this axis that reflect elements of a mammalian body plan.

Model organisms including mice and zebrafish have previously enabled
scientists to gain some insights into human gastrulation. However, these
models may behave differently to human embryos when the cells start to differentiate. Animal models can respond differently to certain drugs:
the anti-morning sickness drug thalidomide, for example, passed clinical
trials after testing in mice but subsequently led to severe birth defects
in humans. For this reason it is important to develop better models of
human development.

Gastruloids do not have the potential to develop into a fully-formed
embryo.

They do not have brain cells or any of the tissues needed for implantation
in the womb. This means they would never be able to progress past the
very early stages of development, and therefore conform to current
ethical standards.

By looking at which genes were expressed in these human gastruloids
at 72 hours of development, the researchers found a clear signature of
the event that gives rise to important body structures such as thoracic muscles, bone and cartilage, but they do not develop brain cells.

The researchers judged the equivalent human embryonic age of
the gastruloids by comparing them to the Carnegie Collection of
Embryology. This official collection contains a continuum of human
embryos, including day-by-day growth over the first eight weeks. They
suggest that gastruloids partially resemble 18-21 day old human embryos.

"This is a hugely exciting new model system, which will allow us to reveal
and probe the processes of early human embryonic development in the lab
for the first time," said Dr Naomi Moris in the University of Cambridge's Department of Genetics, and first author of the report. "Our system is
a first step towards modelling the emergence of the human body plan,
and could prove useful for studying what happens when things go wrong,
such as in birth defects."

========================================================================== Story Source: Materials provided by University_of_Cambridge. Original
written by Jacqueline Garget. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Naomi Moris, Kerim Anlas, Susanne C. van den Brink, Anna Alemany,
Julia
Schro"der, Sabitri Ghimire, Tina Balayo, Alexander van Oudenaarden,
Alfonso Martinez Arias. An in vitro model of early anteroposterior
organization during human development. Nature, 2020; DOI:
10.1038/s41586- 020-2383-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200611094129.htm

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