Order from noise: How randomness and collective dynamics define a stem
cell
Collective cell dynamics could define stem cells identity, number, and dynamics

Date:
July 6, 2020
Source:
Institute of Science and Technology Austria
Summary:
Without stem cells, human life would not exist. Due to them, a
lump of cells becomes an organ, and a fertilized egg develops into
a baby. But what actually makes a stem cell? Are these a stable
population of specially gifted cells? Scientists discovered that
instead, stem cells might emerge due to the collective behavior
of cells within the organs.



FULL STORY ========================================================================== Without stem cells, human life would not exist. Due to them, a lump of
cells becomes an organ, and a fertilized egg develops into a baby. But
what actually makes a stem cell? Are these a stable population of
specially gifted cells? Scientists discovered that instead, stem cells
might emerge due to the collective behavior of cells within the organs.


==========================================================================
Stem cells are central to organ development and renewal. In most
organs, stem cells are located in specific regions and, in some cases,
can be identified through several intrinsic properties, like molecular
markers. They can differentiate into various types of cells and divide indefinitely to produce more stem cells. However, does this mean the
stem cell at the top is immortal? Or can any cell overthrow this? The scientific community is in an open debate whether stem cells actually
arise from intrinsic cell properties or from the collective dynamics
of the tissue itself. In this second scenario, potential stem cells
are in constant competition to sit in certain "niche" regions. Each
cell wants to overtake its neighbor by replication and, therefore,
continuously pushes them. The functional stem cell will be the one that
wins this competition, while losers will be pushed away from the niche, differentiate, and ultimately die.

Here, the Hannezo group at IST Austria looked at the mechanism to
overcome such pushing forces away from the niche, in collaboration with researchers from the National Cancer Institute of Netherlands and the University of Cambridge. They used a live-imaging microscope to record
stem cell movements in the breast, intestine, and kidney tissue. The team
found that in addition to constant flow and pushing forces, many random movements were observed. Why would those be important? "A famous saying
in real estate business is "location, location, location." In the case
of stem cells, this saying transfers to a location determining stemness
(rather than the other way around). Then, random movements become key,
as they allow you to get to the right location even if you started in
the wrong one." summarizes Edouard Hannezo.

Under that framework, the tissues look like the exit of the subway
station in the rush hour, with some people able to randomly turn back
against the drift of the mass, trying to take the subway again. Under
this metaphor, random movements are key to allow cells away from the
stem cell niche to eventually go back to it. "We wanted to know what
defines the number and dynamics of the stem cells, and to what extent
this could be answered by mathematically exploring only the movements of
the cells and the geometry of the organs," says Bernat Corominas-Murtra,
the leading scientist in this study. They then mathematically mapped this
noisy cell dynamics into the geometry of the organs and could predict,
among others, the number of functional stem cells (the ones that can
get to the right location in time, given the amount of noise/mobility
in the system). They found that during tissue renewal or growth, stem
cell regions developed naturally, without needing to make assumptions
on the molecular nature of the cells. Therefore, the scientists showed
that the dynamics and geometry alone play an essential role.

Bernat Corominas-Murtra describes their results: "You would expect that
the randomness of cell movements blurs the properties of the system
or makes it more unstable. Instead, it is key for the emergence of
robust, complex patterns like the stem cell region, which remarkably
coincides with the one previously identified using biomolecular markers
of individual cells." These results contribute to the open debate on the
nature of stem cells in tissues and potentially opens a new dimension
in the understanding of organ renewal.


========================================================================== Story Source: Materials provided by Institute_of_Science_and_Technology_Austria. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Bernat Corominas-Murtra, Colinda L. G. J. Scheele, Kasumi Kishi,
Saskia
I. J. Ellenbroek, Benjamin D. Simons, Jacco van Rheenen, Edouard
Hannezo.

Stem cell lineage survival as a noisy competition for niche access.

Proceedings of the National Academy of Sciences, 2020; 201921205
DOI: 10.1073/pnas.1921205117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200706113957.htm

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