Cell Stem Cell: A biological pathway that causes stem cells to die or regenerate

A new study led by Cedars-Sinai and the University of California, San Francisco (UCSF) has established that altering cellular processes can cause stem cells (cells in which other cells in the body develop) to die or regenerate
.

The findings, published in the peer-reviewed journal Cell Stem Cell, may help develop new drugs that can control this process, slow or stop cancer growth and spread, and regenerate
in the context of other diseases.

Ophir Klein, MD, senior author of the study, said the findings underscore the need for the body to produce the right amount of new cells
.

Klein said: "If you have too many cell divisions, you end up with tumors
.
If you have too few cells, cell replacement can't keep up
.
”

Human cells are regulated
by various biological pathways.
Each pathway involves a series of molecular activities within the cell that produce changes within the cell, such as the creation of a new molecule, such as a protein
.

In the study, researchers at Cedars-Sinai University and the University of California, San Francisco, looked at the effects
of a gene called disc large 1 (DLG1) on the Wnt signaling pathway.
This pathway involves a series of molecular interactions
that regulate the growth or death of stem cells.

The Wnt pathway begins on the cell surface and ends inside the cell and is essential
for stem cell renewal and tissue regeneration.
Although this pathway has been extensively studied, there are still many unknowns
about how small increases and decreases in the frequency of communication signals passing through this pathway affect the production of new cells.

"Signals or indications can vary
over time in different health and disease conditions," Klein said.

The researchers studied intestinal tissue samples from laboratory mice to understand how mutations in Dlg1 affect Wnt signaling and interactions between highly regenerative gastrointestinal stem cells
.
By analyzing the gene expression of the samples, the team looked for changes
in genes that normally send signals along the Wnt pathway.

Through this process, the researchers were able to see how changes in signal frequency affected stem cell generation
.
The researchers found that when they inhibited Dlg1 expression and then increased signaling along the Wnt pathway by adding specific molecules, such as viruses or drugs, the stem cells died instead of producing new daughter cells
.

"By better understanding cell signaling, we can learn how to use molecules to speed up or slow down this pathway and normalize the signaling so that a given organ has the right number of cells," said Genentech, Inc.
, co-first author of the study.
Lead scientist Dr David Castillo-Azofeifa said
.
Castillo-Azofeifa is a postdoctoral researcher
in Klein's lab at the University of California, San Francisco.

"Correct interpretation of signal levels is critical for stem cell survival.
"

The researchers next plan to study the role of the Wnt pathway and Dlg1 in human gut samples to see if they replicate what was observed in laboratory mice
.

Klein previously directed the Institute of Human Genetics and served as head of UCSF's Division of Medical Genetics and Craniofacial Anomalies, where he remains an adjunct professor

Funding: This study was funded by the National Institutes of Health (grants R35-DE026602, R35-GM136348, K99-AG071933, and U01DK103147).