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A Bcl11a-driven mechanism maintaining hematopoietic stem cell functionality gives rise to dysfunction during aging [ATAC-Seq]

GSE266507 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2026/05/17 Platform GPL24247
Summary
Preserving hematopoietic stem cell (HSC) functionality is crucial for sustaining healthy blood and immune system throughout life. However, the mechanisms underlying HSC dysfunction and disruption of hematopoiesis during aging remain unclear. Utilizing an inducible mosaic mouse model, we discovered that Bcl11a levels increase in HSCs with age, mitigating functional decline while also promoting myeloid cell and IL-1β production in the bone marrow, thus accelerating HSC attrition non-cell autonomously. Notably, aging-related inflammation augments the expressions of both Bcl11a and Fc receptors (FcRs) in HSCs. FcR signaling activation induces HSC differentiation, which is counteracted by Bcl11a through repressing FcRγ expression to maintain HSC function. Deletion of FcRγ in Bcl11a-mosaic mice abolishes the non-cell autonomous effect on deteriorating HSCs. Overall, this study unveils the complex nature of HSC aging and underscores the significance of fine-tuning Bcl11a levels and FcRγ signaling strength for hematopoietic regeneration on demand and healthy blood production with age.
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Direct links to NCBI, no account and no request form: the whole study as GSE266507_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1107475 and SRA study SRP505622. Searching any of these in the dataset finder brings you back here.

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