Tag

Hspcs

All articles tagged with #hspcs

science14 days ago•85 min saved

Telomeric DDR blockade rejuvenates aging hematopoiesis

Therapeutic inhibition of telomeric DNA damage response using telomeric antisense oligonucleotides (tASO) suppresses tDDR signaling in telomerase-deficient mice and physiologically aged mice, reducing cellular senescence and inflammation, restoring hematopoietic tissue architecture, enhancing hematopoietic stem/progenitor cell quiescence and fitness, and improving in vivo repopulation and humoral immune responses; ex vivo human aged CD34+ HSPCs also show improved clonogenic potential. Telomere length is unchanged, indicating relief of dysfunction via tDDR blockade rather than telomere elongation, suggesting tDDR inhibition as a therapeutic strategy for telomere biology disorders and age-related hematopoietic aging.

via Nature|

#hematopoietic-aging #hspcs #science

science5 months ago•71 min saved

Skull bone marrow drives immunotolerance in pediatric brain tumors

New research reveals a skull bone marrow–tumor immune axis in childhood brain cancers: CSF-borne signals educate skull hematopoietic stem and progenitor cells to present tumor antigens via MHC-II, polarizing CD4+ T cells toward regulatory T cells and promoting immunotolerance. Disrupting this axis—by normalizing CSF cytokines, mobilizing skull hematopoiesis, or blocking GM-CSF signaling with mavrilimumab (and even more so when combined with immune checkpoint blockade)—induces tumor regression in mouse models of ZFTA–RELA ependymoma, choroid plexus carcinoma, and group 3 medulloblastoma. The findings identify a skull-tumor immunological interface and suggest targeting local skull hematopoiesis as a potentially less-toxic therapy for aggressive pediatric brain tumors.

via Nature|

#csf #hspcs #immunotolerance