Stem cells taking out the garbage. A key to keeping stem cells happy is keeping protein homeostasis. Previous work showed that stem cells, consisting of HSCs, synthesize proteins much slower than other cell types, prioritizing quality over quantity. Stem cells are less interested in constructing new proteins. Hence the authors suggest that by keeping a collection of damaged proteins in one place, stem cells might be developing their own cache of resources that can be used at a later time when they are really needed, such as after an injury or when it is time to regenerate.
The research study concentrated on hematopoietic stem cells (HSCs), the cells in our bone marrow that produce brand-new blood and immune cells throughout our lives. When their function is deteriorated or lost, this can result in blood and immune conditions, such as anemia, blood clotting, and cancer.
UC San Diego researcher Robert Signer, Ph.D., describes how stem cells contribute to aging and age-related diseases. Credit: UC San Diego Health Sciences
” Stem cells are in it for the long haul,” stated senior research study author Robert Signer, Ph.D., associate teacher at UC San Diego School of Medicine. “Their need for durability requires them to be wired in a different way than all the short-lived cells in the body.”
A key to keeping stem cells pleased is maintaining protein homeostasis. Previous work showed that stem cells, consisting of HSCs, manufacture proteins much slower than other cell types, prioritizing quality over amount. This helps them make fewer mistakes in the process, as misfolded proteins can become poisonous to cells if enabled to develop.
Still, some errors or protein damage are unavoidable, so the researchers set out to understand how stem cells make sure these proteins are appropriately discarded.
In the majority of cells, harmed or misfolded proteins get individually tagged for disposal. A mobile protein destroyer called the proteasome then discovers the labeled proteins and breaks them down into their initial amino acid elements. In the brand-new study, the researchers found proteasome activity was particularly low in HSCs. This left the group puzzled: if getting rid of damaged proteins is so crucial to stem cells, why is the proteasome less active?
UC San Diego scientists discovered misfolded proteins were aggregated and caged into a single area (green) within stem cells before being dealt with. Credit: UC San Diego Health Sciences
Through a series of subsequent experiments, the team found that HSCs utilize a various system entirely. Here, damaged and misfolded proteins are collected and trafficked into clusters called aggresomes. When corralled into a single place, they can be collectively destroyed by the lysosome (a cell organelle including digestive enzymes) in a process called aggrephagy.
” Whats really unusual here is this pathway was believed to just be set off as an extreme stress response, but its actually the regular physiological pathway thats utilized by stem cells,” stated Signer. “This highlights how crucial it is for stem cells to prevent stress so they can preserve their health and longevity.”
Why this various system? A main advantage of the proteasome method is that it breaks proteins down instantly, producing amino acids that the cell can recycle to build new proteins. Stem cells are less interested in developing brand-new proteins. Therefore the authors suggest that by keeping a collection of damaged proteins in one location, stem cells may be creating their own cache of resources that can be used at a later time when they are actually needed, such as after an injury or when it is time to regenerate.
” The body actually cant risk losing its stem cells, so having this stockpile of basic materials makes them more safeguarded against rainy days,” said Signer. “Stem cells are marathon runners, however they likewise need to be first-rate sprinters when the circumstances call for it.”
When the scientists genetically disabled the aggrephagy pathway, the stem cells started to collect aggregated protein, which impaired their physical fitness, longevity and regenerative activity.
The team then discovered that while practically all young stem cells had aggresomes, at a certain point in aging, they were nearly completely gone. The authors recommend that stem cells failure to efficiently destroy misfolded proteins during aging is likely a crucial contributing factor to their decreasing function and the resulting age-related disorders.
” Our hope is that if we can improve stem cells ability to keep the aggrephagy path, we will maintain better stem cell fitness throughout aging and mitigate blood and immune conditions,” stated Signer.
The authors believe that other types of stem cells and long-lived cells like nerve cells have a comparable requirement for stringent policy of protein homeostasis, recommending rehabs to boost this pathway may be useful throughout several organs and pathologies.
Enter your journal: Reference: “Hematopoietic stem cells preferentially traffic misfolded proteins to aggresomes and depend upon aggrephagy to maintain protein homeostasis” by Bernadette A. Chua, Connor J. Lennan, Mary Jean Sunshine, Daniela Dreifke, Ashu Chawla, Eric J. Bennett and Robert A.J. Signer, 21 March 2023, Cell Stem Cell.DOI: 10.1016/ j.stem.2023.02.010.
Co-authors of this research study include: Bernadette A. Chua, Connor J. Lennan, Mary Jean Sunshine, Daniela Dreifke and Eric J. Bennett at UC San Diego and Ashu Chawla at La Jolla Institute for Immunology.
According to a study just recently released in the journal Cell Stem Cell, scientists at the University of California San Diego School of Medicine discovered that blood stem cells use an unexpected strategy to remove their misfolded proteins. The researchers found that this procedure decreases with age and believe that improving this specialized trash disposal system might help ward off age-related health problems.
As human beings continue their look for the water fountain of youth, stem cells keep becoming an essential player in the mission for durability. Research studies increasingly suggest that protecting the physical fitness of stem cells results in a longer healthspan, and brand-new research highlights the importance of keeping stem cells spick-and-span.
Stem cells taking out the trash. This illustration is from Emma Vidal of DrawImpacts. Credit: Emma Vidal
Scientists at UC San Diego have found that stem cells distinct approach of disposing of misfolded proteins might hold the secret to maintaining long-lasting health and preventing illness.