AI Article Synopsis
- Hematopoietic stem cells (HSCs) can regenerate blood cells, but the specific signals that guide them in this process after injury are not well understood.
- During anemia, HSCs take up more iron, which activates genes related to red blood cell production through a mechanism involving the Tet2 protein.
- The study found that HSCs in the spleen increase their numbers and activity in response to anemia, highlighting the critical role of iron in enabling these cells to differentiate into red blood cells.
Article Abstract
Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes DNA demethylation and expression of erythroid genes. Suppressing iron uptake or TET2 expression impairs erythroid genes expression and erythroid differentiation of HSCs; iron supplementation, however, augments these processes. These results establish that the physiological level of iron taken up by HSCs has an instructive role in promoting erythroid-biased differentiation of HSCs.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789814 | PMC |
| http://dx.doi.org/10.1038/s41467-024-44718-0 | DOI Listing |
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