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DKFZ and HI-STEM identify dormant blood stem cell subset in mice

Researchers discovered a murine hematopoietic stem cell subpopulation that remains dormant longer and resists inflammatory stress.

DKFZ and HI-STEM identify dormant blood stem cell subset in mice
Photo: Yahoo Nachrichten DE

Researchers from the German Cancer Research Center (DKFZ) and the stem cell institute HI-STEM in Heidelberg have identified an overlooked population of hematopoietic stem cells in mice, according to Yahoo Nachrichten DE. The findings, published in the journal Cell Stem Cell, show that these cells remain in a state of deep quiescence significantly longer than previously known blood stem cells de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗. After more than 200 days, between 10 and 15 percent of these newly characterized cells retained a low-division marker, compared to roughly 2 percent in standard stem cell populations de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗.

Historically, isolation protocols relied on the CD150 surface marker, which excluded cells lacking this feature. The Heidelberg team found that the newly described population lacks CD150 but expresses the endothelial protein C receptor (EPCR), designating them as LT-HSC2 de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗. The researchers reported that this subset expands the known pool of functional, long-term blood stem cells by more than 15 percent de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗.

Resistance to inflammatory stimuli

The identified cells demonstrated distinct physiological properties during stress testing. When exposed to inflammatory signaling, specifically interleukin-1 and type-I interferon pathways, the LT-HSC2 cells exhibited lower activation rates in mice than conventional hematopoietic stem cells de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗. While frequent division can deplete stem cell reserves, this relative insensitivity to inflammatory cues helps protect their long-term regenerative capacity de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗. However, the exact molecular mechanisms maintaining this pronounced dormant state remain under investigation.

Lineage bias and transplantation

The LT-HSC2 subpopulation primarily differentiates into lymphocytes, the white blood cells responsible for adaptive immunity, while retaining the capability to generate erythrocytes, platelets, and other immune lineages de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗. In serial transplantation experiments in mice, as few as 30 isolated cells reconstituted multiple blood cell lineages for over 48 weeks de.nachrichten.yahoo.comYahoo Nachrichten DEde.nachrichten.yahoo.comOpen source ↗. The capacity persisted through secondary transplantations, and single-cell trials confirmed multi-lineage reconstitution. While the study was conducted entirely in mice, the team noted preliminary indications of a comparable human population, which will serve as the subject of future research.

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