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Protein HSF1 : Promote the Healthy Culture of Stem Cells and Fight Aging

Hematopoietic stem cells(HSC), the precuisor cells of blood cells, have been notoriously difficult to grow in a petri dish.
In a new study, researchers from the University of California, San Diego, and the La Jolla Institute of Immunology discovered the cause of this underlying problem and developed a way to keep hematopoietic cells grown in vitro healthy. The findings are good news for patients seeking hematopoietic stem transplants and point to a new way to fight the aging of hematopoietic stem cells. The results were published online August 12, 2021 in the journal Cell Stem Cell. The title of the paper is“Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging”。
In a bone marrow transplant, hematopoietic stem cells are injected intravenously to rebuild blood production in the bone marrow or in patients with compromised immune systems. The method is used to treat diseases such as leukemia, lymphoma, aplastic and immune deficiency diseases. However, patients who need an infusion of hematopoietic stem cells do not always donated hematopoietic stem cells.
Robert Signer, PHD, corresponding author of the paper and assistant professor at the UNIVERSITY of California, San Diego School of Medicine said that ‘Even in patients treated with hematopoietic stem cells, transplanting more cells produces fewer complications and increases the overall chance of success.’
When scientists tried to grow hematopoietic stem cells by recreating the marrow environment in a petri dish, Signer and his team are questioned about:‘ what internal mechanism caused these stem cells to become unhealthy in the first place, and could they directly remedy the process?’
In the new study, lead author Miriama Kruta,PHD, a postdoctoral researcher in Signer’s lab, and colleagues found that in a foreign environment in a apetri dish, hematopoietic stem cells began to produce excessive amounts of protein, causing extreme stress. This extreme stress state activates the heat shock response, a highly conserved stress-reduction pathway regulated by heat shock factor 1 (HSF1). These authors identified 2 different small molecules:HSP90,tanespimycin(17- AAG) and HSF1 activator (HSF1A), they both can highly activate the HSF1 gene. By adding one of these two small molecules to cultured hematopoietic stem in vitro, increased activity of the heat shock pathway helps to rebalance the homeostasis, or keep the stability.
‘Today, we can preserve high-quality hematopoietic stem cells in vitro for long periods of time,’ Signer said, ‘We hope that this improvement in quality will lead to improve clinical outcomes.’
Restoration of protein homeostasis through enhanced HSF1 activation has been shown in both mouse and human hematopoietic stem cells. Signer said, the next step is to test how these samll molecules affect the results of human hematopoietic stem cells in the transplant system.
These authors found that the heat shock pathways is not only important in petri dishes, it also keeps natural bone marrow hematopoietic stem cells healthy during aging. Although HSF1 is inactive in hematopoietic stem cells of young adults, it is activated in hematopoietic stem cells of middle age and older adults.
Signer said:’ HSF1 is activated during aging to keep your hematopoietic stem cells healthy. Protein damage damages hematopoietic stem cells during aging and may lead to inter ference. Highly activated HSF1 may eventually be used to improve hematopoietic stem cell and tissue function during aging to prevent blood diseases and enhance immunity in the elderly.
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