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Musashi 2 is a regulator of the HSC compartment identified by a retroviral insertion screen and knockout mice
- Source :
- Blood 118, 554-564 (2011)
- Publication Year :
- 2011
-
Abstract
- We used a retroviral integration screen to search for novel genes that regulate HSC function. One of the genes that conferred HSC dominance when overexpressed due to an adjacent retroviral insertion was Musashi 2 (Msi2), an RNA-binding protein that can act as a translational inhibitor. A gene-trap mouse model that inactivates the gene shows that Msi2 is more highly expressed in long-term (LT) and short-term (ST) HSCs, as well as in lymphoid myeloid primed progenitors (LMPPs), but much less in intermediate progenitors and mature cells. Mice lacking Msi2 are fully viable for up to a year or more, but exhibit severe defects in primitive precursors, most significantly a reduction in the number of ST-HSCs and LMPPs and a decrease in leukocyte numbers, effects that are exacerbated with age. Cell-cycle and gene-expression analyses suggest that the main hematopoietic defect in Msi2-defective mice is the decreased proliferation capacity of ST-HSCs and LMPPs. In addition, HSCs lacking Msi2 are severely impaired in competitive repopulation experiments, being overgrown by wild-type cells even when mutant cells were provided in excess. Our data indicate that Msi2 maintains the stem cell compartment mainly by regulating the proliferation of primitive progenitors downstream of LT-HSCs.
- Subjects :
- Male
Myeloid
hematopoietic stem-cells
binding protein musashi
in-vivo
mammalian cns
gene-transfer
c/ebp-alpha
c-myc
rna
proliferation
expression
Immunology
Molecular Sequence Data
Regulator
Thymus Gland
Biology
Biochemistry
Leukocyte Count
Mice
Cell Movement
Gene expression
medicine
Cell Adhesion
Animals
Genetic Testing
Progenitor cell
Gene
Myeloid Progenitor Cells
Mice, Knockout
Protein Synthesis Inhibitors
RNA-Binding Proteins
Neomycin
Cell Biology
Hematology
Lymphoid Progenitor Cells
beta-Galactosidase
Molecular biology
Mice, Inbred C57BL
Haematopoiesis
Mutagenesis, Insertional
medicine.anatomical_structure
Retroviridae
Knockout mouse
Female
Stem cell
Cell Division
Spleen
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 118
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....6fdef9c7c6c3fde2effbc11d84e3b85c