Unknown

Dataset Information

0

Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment.

ABSTRACT: Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice. Our results reveal cellular heterogeneity in the onset of HSC aging and implicate a role for JAK2V617F-driven proliferation in the p53-mediated functional decline of old HSCs.

SUBMITTER: Kirschner K 

PROVIDER: S-EPMC5457484 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and  ...[more]

Similar Datasets

Unknown Megakaryocyte progenitor cell function is enhanced upon aging despite the functional decline of aged hematopoietic stem cells.
| S-EPMC8190594 | biostudies-literature
Unknown Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation.
| S-EPMC1925137 | biostudies-literature
Unknown Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment.
| S-EPMC5896201 | biostudies-literature
Transcriptomics Replication Stress is a Potent Driver of Functional Decline in Aging in Hematopoietic Stem Cells
2014-07-14 | GSE48893 | GEO
Unknown A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells.
| S-EPMC2424153 | biostudies-literature
Unknown Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche.
| S-EPMC6095812 | biostudies-literature
Unknown Vascular adhesion protein-1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation.
| S-EPMC8629906 | biostudies-literature
Transcriptomics Megakaryocyte Progenitor Cell Function is Enhanced Upon Aging Despite the Functional Decline of Aged Hematopoietic Stem Cells
2021-06-01 | GSE166704 | GEO
Unknown Loss of ATF4 leads to functional aging-like attrition of adult hematopoietic stem cells.
| S-EPMC8694622 | biostudies-literature
Unknown FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia.
| S-EPMC7656925 | biostudies-literature