Scientists have reported new discoveries into how stem cells lose their self-renewal ability over the life course.
Dr Andreas Trumpp of the German Cancer Research Centre, Heidelberg, Germany, and colleagues have examined the way in which blood stem cells maintain their ability to self-renew.
Using mice, they found that the stem cell niche produces a molecule called netrin-1 that stimulates the ability of blood stem cells to make copies of themselves or self-renew. Netrin-1 was produced on the tiny blood vessels in the bone marrow. They also found that, during ageing, production of this factor decreases.
Their research was published recently in the journal Nature Communications.
Dr Trumpp says: “The dormancy is the prerequisite for this unique ability of stem cells. The almost unlimited self-renewal capacity is considered a key property of the very rare stem cells, which play a central role in the maintenance and repair of tissues and organs.
“However, cancer cells also possess this ability. They either derive directly from stem cells or acquire this ability through genetic modification. Without self-renewal, there is no cancer.”
The researchers found that the surface of dormant blood stem cells carries large amounts of neogenin-1 – the receptor protein for netrin-1. The team describe neogenin-1 as a key molecule for self-renewal, as it is only found on blood stem cells.
When the neogenin-1 receptor is genetically switched off, stem cells no longer stay dormant and lose their ability to self-renew. But when it was increased, they “slept all the more deeply,” the authors add.
Ultimately, the researchers discovered that the interaction between neogenin-1 on the stem cells and netrin-1 in the stem cell niche was crucial for stem cell function. They found that as mice age, the amount of netrin-1 in the niche decreases, which led to decreased blood stem cell function over time.
“Our results reconfirm the central role of the stem cell niche for stem cell function and thus for the regenerative capacity and health of our body,” Dr Trumpp concludes.
Renders S, Svendsen AF, Panten J, Rama N, Maryanovich M, Sommerkamp P, Ladel L, Redavid AR, Gibert B, Lazare S, Ducarouge B, Schönberger K, Narr A, Tourbez M, Dethmers-Ausema B, Zwart E, Hotz-Wagenblatt A, Zhang D, Korn C, Zeisberger P, Przybylla A, Sohn M, Mendez-Ferrer S, Heikenwälder M, Brune M, Klimmeck D, Bystrykh L, Frenette PS, Mehlen P, de Haan G, Cabezas-Wallscheid N, Trumpp A. (2021) “Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1.” Nature Communications, doi: 10.1038/s41467-020-20801-0
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