Overturning the single stem cell theory: a second stem cell was found in the mammalian brain

In the brains of adult mammals, neural stem cells guarantee the constant formation
of new nerve cells, i.
e.
neurons.
This process, known as adult neurogenesis, helps mice maintain their sense of
smell.
A team led by Dr.
Francesca Ciccolini of the Interdisciplinary Neuroscience Centre (IZN) at the University of Heidelberg recently discovered a second stem cell population in mouse brains
.
This new type of stem cell, rather than the previously known one, is primarily involved in the production
of new neurons in the olfactory bulb of adult mice.

So far, scientific research on neurogenesis has focused on
so-called apical stem cells.
Dr.
Ciccolini explains: "They have long been considered the only stem cell population in the brains of adult mice and are the main driver of nerve cell formation
.
" These neural stem cells are located in the subventricular region near the lateral ventricles
.
They were once thought to form precursor cells that then differentiate in the olfactory bulb of mice into interneurons, nerve cells that regulate the transmission of stimuli between interconnected neurons
.
Researchers at the University of Heidelberg have overturned the theory of a single stem cell type and the hypothesis that
apex stem cells are responsible for neurogenesis.

Initially, researchers in the Department of Neurobiology were studying how so-called solitary stem cell populations in mouse brains behave
in different situations.
They used genetically modified animals whose neural stem cells were stained green
by dyes active in the nucleus.
Neurobiologists were surprised to find that most green cells did not show the characteristics
of known vertex stem cells.
"At first, we thought they might be astrocytes, helping cells make sure neurons are able to do their job
.
But after we did some functional analysis, it quickly became clear that this is definitely an independent stem cell population," Dr.
Ciccolini emphasizes
.

Further research showed that the newly discovered stem cell types differed morphologically and functionally from
known populations.
Such cells are not in contact with the lateral ventricles and are therefore called basal cells
.
The researchers determined that basal stem cells — not vertex stem cells — were responsible for the formation
of olfactory bulb neurons.
To prove this, they labeled two cell populations separately and then observed whether the labeled neurons appeared in the
olfactory bulb.
Francesca Ciccolini explains: "This only happens when
the underlying population is tagged.
" When only vertex stem cells are labeled, new labeled neurons cannot be detected in the olfactory bulb
.

Scientists at the University of Heidelberg also found that stem cell types and precursor cells in mouse brains communicate with
each other through so-called notch interactions.
A receptor of the same name plays a crucial role in controlling the rate of cell proliferation and monitoring the process of
cell differentiation.
Katja Baur, a PhD researcher on Francesca Ciccolini's working group, explains: "The activity of the gap determines whether the stem cells are still stem cells or develop into nerve cells
.
" She added: "We suspect that vertex stem cells intervene in the activation of notch signaling pathways, which can inhibit proliferation and neurogenesis
.
" In addition to this, it prevents the depletion
of the stem cell bank.

Dr Ciccolini emphasized: "We found that there is another stem cell type in the mouse brains of adult animals, which provides new clues
to the process of neuronal formation.
" The human brain has similar stem cells, which are involved in the formation
of brain tumors.
The researchers at the University of Heidelberg hope that their work will also provide new clues
to the development and possible treatment of such tumors.

Katja Baur, Yomn Abdullah, Claudia Mandl, Gabriele Hö lzl‐Wenig, Yan Shi, Udo Edelkraut, Priti Khatri, Anna M Hagenston, Martin Irmler, Johannes Beckers, Francesca Ciccolini.
A novel stem cell type at the basal side of the subventricular zone maintains adult neurogenesis.
EMBO reports, 2022; 23 (9)