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October 9, 2025BloodOpen Access

A Notch trans-activation to cis-inhibition switch underlies hematopoietic stem cell aging

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Decreased Notch signaling in aged HSCs leads to reduced regenerative potential.
Sinusoidal Jagged2 deletion replicates aging effects on HSCs, promoting myeloid-biased lineage.
Cis-inhibition of Notch by Jagged2 upregulation results in reduced hematopoietic regeneration.
Crosstalk between BM niche and HSC intrinsic features regulates HSC fate priming.

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Research shows Notch signaling impacts HSC fate and regenerative capacity in aging, highlighting the role of Jagged2.

Matteini et al. (2025) studied this question.

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