Back to Search
Start Over
Bmi1 counteracts hematopoietic stem cell aging by repressing target genes and enforcing the stem cell gene signature
- Source :
- Biochemical and Biophysical Research Communications. 521:612-619
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Polycomb-group proteins are critical regulators of stem cells. We previously demonstrated that Bmi1, a component of polycomb repressive complex 1, defines the regenerative capacity of hematopoietic stem cells (HSCs). Here, we attempted to ameliorate the age-related decline in HSC function by modulating Bmi1 expression. The forced expression of Bmi1 did not attenuate myeloid-biased differentiation of aged HSCs. However, single cell transplantation assays revealed that the sustained expression of Bmi1 augmented the multi-lineage repopulating capacity of aged HSCs. Chromatin immunoprecipitation-sequencing of Bmi1 combined with an RNA sequence analysis showed that the majority of Bmi1 direct target genes are developmental regulator genes marked with a bivalent histone domain. The sustained expression of Bmi1 strictly maintained the transcriptional repression of their target genes and enforced expression of HSC signature genes in aged HSCs. Therefore, the manipulation of Bmi1 expression is a potential approach against impairments in HSC function with aging.
- Subjects :
- 0301 basic medicine
Aging
Biophysics
macromolecular substances
Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Proto-Oncogene Proteins
medicine
Animals
Myeloid Cells
Molecular Biology
Gene
Cellular Senescence
Polycomb Repressive Complex 1
biology
Hematopoietic stem cell
Cell Biology
Gene signature
Hematopoietic Stem Cells
Hematopoiesis
Cell biology
Chromatin
Haematopoiesis
030104 developmental biology
Histone
medicine.anatomical_structure
Gene Expression Regulation
BMI1
030220 oncology & carcinogenesis
biology.protein
Stem cell
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 521
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....9a964faad1e86d913aa56da0740b5448