A mouse embryo that has gathered the efforts of the entire laboratory for more than ten years, tells the world another miracle of life

In the Embryology and Stem Cell Laboratory of the University of Cambridge, a mouse embryo, which has gathered the efforts of the entire laboratory for more than ten years, tells the world another miracle of life

▲Professor Magdalena Zernicka-Goetz of the University of Cambridge, who also works at the California Institute of Technology (Photo credit: Simon Zernicki-Glover)

▲Professor Magdalena Zernicka-Goetz of the University of Cambridge, who also works at the California Institute of Technology (Photo credit: Simon Zernicki-Glover)

The use of stem cells to synthesize mouse embryo models is not news in itself

A "Cell" paper

Reported mouse embryos that not only do not require sperm and egg cells, but even grow directly in an "artificial uterus"

Just now, this blockbuster result was published in the top academic journal "Nature"

We know that embryonic stem cells (ESCs) play a key role from the fertilized egg to the birth of new life into the world

embryonic stem cells

But to form a complete embryo, only embryonic stem cells are not enough

Two structures that support embryonic development are also integral: the placental yolk sac

The placenta and yolk sac differentiate from two types of extraembryonic stem cells: trophoblast stem cells (TSC) and extraembryonic endoderm stem cells (XEN)

trophoblast stem cells extraembryonic endoderm stem cells

Therefore, to artificially create a complete mouse embryo, the joint participation of these three kinds of stem cells is indispensable

Such embryos cannot form the neural tube, the primitive structure that differentiates into the brain and spinal cord, and naturally do not have a clear brain structure

▲The research of Professor Zernicka-Goetz's team in 2017 used two kinds of stem cells to synthesize mouse embryos (Image source: Reference [3])

▲The research of Professor Zernicka-Goetz's team in 2017 used two kinds of stem cells to synthesize mouse embryos (Image source: Reference [3])

Of course, for scientists, the task is not only to put these three kinds of stem cells together, but also to make them "talk" smoothly

In the latest study, the research team used a combination of mouse embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells (iXEN)

Embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells

Eventually, these stem cells self-organize into embryos and continue to develop until neural tube formation

These stem cells self-organize into embryos and continue to develop until neural tube formation

▲Comparison of natural (top) and synthetic (bottom) mouse embryos, the brain and heart structures of both can be seen (Image source: Amadei and Handford)

▲Comparison of natural (top) and synthetic (bottom) mouse embryos, the brain and heart structures of both can be seen (Image source: Amadei and Handford)

What organ structures have been differentiated from the embryonic model at this time? Under the microscope, the research team observed the neural tube, the continuously beating heart structure, the gut tube, the primordial germ cells, the tail bud region containing the precursor cells of the neuromesoderm.

The complete brain structure can be discerned between the forebrain and midbrain regions

▲The embryo model successfully developed to the equivalent of the 8th day of the mouse embryo (Image source: Reference [1])

▲The embryo model successfully developed to the equivalent of the 8th day of the mouse embryo (Image source: Reference [1])

Having a complete structure does not imply the same function as a real embryo

Embryonic models in which Pax6 was knocked out also displayed a similar pattern of defects
.

This result means that the artificial embryo model can simulate the neural development in real embryos, so in the future scientists may no longer use model animals, but directly analyze the genetic factors that regulate development in artificial embryos, and study many in brain development.
Genes with unknown function
.

Directly analyze the genetic factors that regulate development in artificial embryos, and study many genes whose functions in brain development are not yet clear
.

“Stem cell embryo models are important because they give us access to the early stages of embryonic development
.
When tiny embryos implant in the uterus, a hidden period that we cannot see (with traditional methods)
.
This accessibility allows us to manipulate genes, to understand their role in the development of model systems,
" said Professor Zernicka-Goetz
.

▲ Another schematic diagram of natural (top) and synthetic (bottom) mouse embryos (Image source: Amadei and Handford)

▲ Another schematic diagram of natural (top) and synthetic (bottom) mouse embryos (Image source: Amadei and Handford)

In addition, this model can help researchers understand why some embryos fail to develop smoothly, and guide the artificial synthesis of human organs, providing a new potential source for organ transplantation
.
Currently, the research team is developing similar human embryo models, which they hope to use to synthesize specific organs
.

Guide the artificial synthesis of human organs and provide new potential sources for organ transplantation
.

"There are countless people around the world waiting for organs to be transplanted," said Professor Zernicka-Goetz, "and the knowledge gained from this work could be used to 'grow' human organs, saving countless lives
.
" The ethical issues that may arise, this breakthrough technology will undoubtedly bring a powerful new weapon to future medical and genetic research
.

Regarding the prospect of human embryo models, Professor Alfonso Martinez Arias of Pompeu Fabra University in Spain said that the efficiency and reliability problems in mouse studies must be solved first, so it will take some time to realize
.
But "the results of this study suggest that similar experiments will be carried out in human cells in the future; at some point, similar results will appear
.
So people need to think about the ethical and social implications of these studies before they arrive
.
" "