Stem cells do not (only) play dice
Stem cells work as a team and do not leave their fate to pure chance


Date:
November 8, 2021
Source:
Max Planck Institute of Molecular Physiology
Summary:
In just a few weeks a completely new organism develops from a
fertilized egg cell. The real miracle is that a bunch of identical
stem cells turns into completely different, specialized cell
types. A team has now been able to show that the specialization of
individual cells during embryonic development is not, as previously
assumed, exclusively left to chance but is rather determined by
cell communication.



FULL STORY ==========================================================================
Stem cells are true multi-talents. They can develop into any cell type
of an organism -- in humans there are over 200 -- and thus perform all
vital tasks.

Once the stem cells have decided on a task they can no longer be deterred
from their goal. The final product, tissues and organs, almost always
look the same and consist of defined proportions of different specialised
cell types. But how do the cells actually know what they want to become
and how many of them are actually allowed to do so?

==========================================================================
Is it all just chance? An important regulator of the distribution of
tasks is the control of genes by transcription factors such as NANOG
and GATA, which are both initially present in the undifferentiated stem
cells. This changes fundamentally, however, in the very early development
when the stem cells develop into two new cell types: Cells of the early
embryo, in which now only NANOG is present and precursor cells of the
fruit bladder which now exclusively carry GATA. Until now, it was thought
that the decision of each individual cell was made rather randomly at
an early stage, similar to a dice game, except that here only NANOG or
GATA can be rolled.

Cells decide collectively In a previous theoretical paper, Aneta Koseska, co-author of the study and former MPI group leader, was able to establish
a new concept with the help of Christian Schro"ter, showing how stem
cells specialize in right proportions in a coordinated manner. In
the current publication, Christian Schro"ter and his team have now
succeeded in substantiating the theoretical concept. Using stem cells
in a test tube, the researchers were able to show that decision-making
does not take place purely randomly at the level of individual cells,
as previously assumed, but is communicated within the cell community.

Cheating at the stem cell dice game In order not to leave the fate of the
cells to chance, the researchers manipulated the NANOG-GATA dice in their investigations so that GATA is now rolled more often than NANOG. This
was achieved experimentally by artificially increasing the amount of
GATA. Even though a six was always rolled -- i.e. GATA -- the number
of fruit bladder precursor cells could not be arbitrarily increased,
but similar proportions of the two different cell types continued to
emerge. The distribution of tasks during development must therefore be dependent on more than mere chance.

Decisions are communicated in the team Following their theoretical
concept, the scientists investigated the role of cellular communication
in embryonic development. As a central means of communication cells
use messenger substances such as growth factors, which they produce
and secrete themselves. These substances are then received by other
cells and control their specialization. If the researchers took away a
growth factor that was important for cell development, the cells were
no longer able to develop into fruit bladder precursor cells even in
the presence of high amounts of GATA. However, the more of the growth
factor the cells received, the more fruit bladder precursor cells also developed. Their ability to divide into the right proportions of the
two cell types despite disturbances was thus lost.

Stem cells must therefore communicate with each other in order to make
the right decision.

"Communication in cell development is like working in a team. If
the members choose tasks without consulting each other, some things
are done twice and others not at all. A team that communicates well,
on the other hand, can solve problems that arise and complete even
complex projects reliably and efficiently," Christian Schro"ter
says. "So it's not just the state of the individual cell that decides
on its faith, but the functioning communication with the other cells." ========================================================================== Story Source: Materials provided by Max_Planck_Institute_of_Molecular_Physiology. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Dhruv Raina, Azra Bahadori, Angel Stanoev, Michelle Protzek, Aneta
Koseska, Christian Schro"ter. Cell-cell communication through FGF4
generates and maintains robust proportions of differentiated cell
types in embryonic stem cells. Development, 2021; 148 (21) DOI:
10.1242/ dev.199926 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211108130842.htm

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