Epigenetic regulation of hematopoietic stem cells during aging and post dietary intervention

Age-associated hematopoietic stem cell (HSC) dysfunction involves dramatic transcriptional changes, but whether specific transcripts orchestrate HSC aging phenotypes remains unclear. We performed epigenetic profiling to investigate the regulatory mechanisms underlying HSC aging. Dysregulated 3D chromatin organization, altered histone modifications, and changed chromatin accessibility shaped the altered transcriptome. We identified a novel looping structure between part of Btaf1 and the whole Ide gene in old HSCs, accompanied by overexpression of a shorter Btaf1 variant (nBtaf1). Mechanistically, elevated nBtaf1 drives aging-associated overexpression of HSC- and megakaryocyte progenitor (MkP)-related genes by regulating TBP promoter binding, contributing to HSC expansion and elevated MkP production in aged mice. nBtaf1 knockdown restores a younger HSC transcriptome and represses these phenotypes, revealing a novel variant that contributes to HSC aging.

Hosted by Carolina Florian – Stem Cell Aging group

Isabel Beerman, PhD, is a Senior Investigator in the Translational Gerontology Branch at the National Institute on Aging (NIA/NIH), where she leads research on the epigenetic mechanisms driving stem cell aging. She earned her PhD in Genetics from Yale University and AB in Biochemistry from Harvard, and completed postdoctoral training in stem cell biology at Harvard Medical School with Derrick Rossi. Her lab uses integrated multi-omics to define how chromatin reorganization, DNA methylation, and histone modifications reshape the aging stem cell transcriptome, and to test aging interventions—such as caloric restriction and NAD+ supplementation—to mitigate age-related decline.