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SUMMARY:Integrated epigenomics reveal dysregulated chromatin landscapes in
  aged hematopoietic stem cells underlying aberrant transcription - Dr Isab
 el Beerman
DTSTART:20220912T150000Z
DTEND:20220912T170000Z
UID:TALK178166@talks.cam.ac.uk
CONTACT:107261
DESCRIPTION:Age-associated hematopoietic stem cell (HSC) phenotypes contri
 bute to myeloid lineage skewing\, loss of reconstitution potential\, and e
 levated risk of cancer transformation. To define specific epigenetic alter
 ations associated with changed potential in old HSCs\, we profiled transcr
 iptomes\, histone modifications\, chromatin accessibility\, and chromatin 
 interactions of purified HSCs from young and aged mice. Uniquely\, we have
  used a consistent immunophenotype to isolate stem cells and updated metho
 dology to generate a compendium of epigenetic analyses to serve as a resou
 rce for studying the regulation of hematopoietic stem cells. Aged HSCs had
  globally decreased levels of active\, permissive\, and repressive histone
  modifications compared to young HSCs\, though specific loci displayed age
 -associated increases. We classified HSC bivalent promoters with presence 
 of both H3K27me3 and K3K4me3\, and approximately twenty percent of domains
  had significant age-associated alterations with almost half of the modifi
 ed bivalent promoters associated with HSC transcriptional alterations. The
  histone modification changes were accompanied by an overall more open chr
 omatin landscape allowing for increased accessibility at functionally rele
 vant transcription factor binding sites and aberrant expression of transpo
 sable elements in aged HSCs. The increased chromatin accessibility in aged
  HSCs was also accompanied by enrichment of H3K27ac levels at putative enh
 ancer regions. Moreover\, the loosened chromatin was associated with incre
 ased short-range and decreased long-range interactions in mostly heterochr
 omatin regions\, measured by Hi-C. These epigenomic data generated on a un
 iformly isolated population of HSCs provide a consensus library on changes
  associated with aging and define critical targets for restoration of yout
 hful potential.\n
LOCATION:Jeffrey Cheah Biomedical Centre\, Cambridge Biomedical Campus\, C
 ambridge
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