Researchers from EMBL Heidelberg
and from the University of Padua School of Medicine have created the first
complete description of early embryo development, accounting for every single
cell in the embryo. This ‘virtual embryo’ will help to answer how the different
cell types in an organism can originate from a single egg cell. The results are
published on 20 April in the journal Cell.
“How are the
many different cell types in the body generated during embryonic development
from an egg, which is only a single cell? This is one of the most fundamental
questions in biology,” explains Dr. Pierre Neveu, group leader at EMBL
Heidelberg, setting out the rationale behind the research he and his group have
performed in collaboration with the group of Dr. Lars Hufnagel.
While answering
this question is essential to understand how multicellular organisms form,
studying the developmental mechanisms driving this cellular diversification at
the single-cell, genome-wide, and whole-embryo level is a challenging task. “So
far we have lacked a comprehensive understanding of the gene expression
programmes. These instruct individual cells to form the different cell types
necessary to build an embryo,” explains Dr. Hanna Sladitschek, first author of
the study — a former postdoc at EMBL Heidelberg and now at the University of
Padua School of Medicine. Despite recent advances in the field, a complete
representation of embryonic development, accounting for every single cell in
space and time, has not been achieved until now.
The EMBL researchers were able to solve this problem by constructing a
‘virtual embryo’ of Phallusia mammillata — a type
of marine organism known as a sea squirt, which is found in the Mediterranean
Sea and the Atlantic Ocean. This species was picked as a model system because
it is related to vertebrates and each individual has the same number of cells,
making it easier to combine observations from many specimens.
This virtual
embryo describes the gene expression and morphology of every single cell of an
embryo at every cell division in the early stages of development — showing the
evolution from a single cell to the 64-cell stage. After these first seven cell
divisions, the fates of the future nerve cord, brain, germ cells, blood cell
precursors, and muscles are already specified. This makes it the first full
description of early development accounting for every single cell in an embryo.
It describes both gene expression — how a cell’s genetic information is
expressed and appears — and spatial position. To generate this comprehensive
atlas, the researchers combined high-resolution single-cell transcriptomics and
light-sheet imaging.
“Our model shows
that it is possible to know the location and history of an individual cell by
analysing its gene expression,” says Neveu. “In addition, we find that while
the regulation of gene expression is very precise within an embryo, differences
in developmental timing explain the observed variation between individual
embryos.”
Gene expression
is generally thought to be a noisy process — in other words, one that shows an
element of randomness — yet the new results show that it is remarkably
reproducible and coordinated across cells in a given embryo. “How is such
coordination achieved? How does the embryo coordinate between the two
mirror-symmetric embryo halves?” says Neveu, highlighting some of the new
questions that the scientists would like to answer.
“Our studies
represent a leap forward in the emerging field of developmental genomics,” says
Hufnagel. “Now that we have worked with an organism with a small number of
cells, it will of course be very interesting to extend our work to mammals,
which have many more cells!”
Source:
No comments:
Post a Comment