PMID- 21613258
OWN - NLM
STAT- MEDLINE
DCOM- 20111007
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 118
IP  - 3
DP  - 2011 Jul 21
TI  - Musashi 2 is a regulator of the HSC compartment identified by a retroviral 
      insertion screen and knockout mice.
PG  - 554-64
LID - 10.1182/blood-2010-12-322081 [doi]
AB  - 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.
FAU - de Andres-Aguayo, Luisa
AU  - de Andres-Aguayo L
AD  - Differentiation and Cancer Program, Center for Genomic Regulation and UPF, 
      Barcelona, Spain.
FAU - Varas, Florencio
AU  - Varas F
FAU - Kallin, Eric M
AU  - Kallin EM
FAU - Infante, Jose F
AU  - Infante JF
FAU - Wurst, Wolfgang
AU  - Wurst W
FAU - Floss, Thomas
AU  - Floss T
FAU - Graf, Thomas
AU  - Graf T
LA  - eng
SI  - GENBANK/GSE29432
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110525
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Msi2h protein, mouse)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - I16QD7X297 (Neomycin)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/physiology
MH  - Cell Division/physiology
MH  - Cell Movement/physiology
MH  - Female
MH  - Genetic Testing/methods
MH  - Leukocyte Count
MH  - Lymphoid Progenitor Cells/cytology/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Mutagenesis, Insertional
MH  - Myeloid Progenitor Cells/cytology/*physiology
MH  - Neomycin
MH  - Protein Synthesis Inhibitors
MH  - RNA-Binding Proteins/*genetics/*metabolism
MH  - Retroviridae/genetics
MH  - Spleen/pathology
MH  - Thymus Gland/pathology
MH  - beta-Galactosidase/genetics
EDAT- 2011/05/27 06:00
MHDA- 2011/10/08 06:00
CRDT- 2011/05/27 06:00
PHST- 2011/05/27 06:00 [entrez]
PHST- 2011/05/27 06:00 [pubmed]
PHST- 2011/10/08 06:00 [medline]
AID - S0006-4971(20)44734-2 [pii]
AID - 10.1182/blood-2010-12-322081 [doi]
PST - ppublish
SO  - Blood. 2011 Jul 21;118(3):554-64. doi: 10.1182/blood-2010-12-322081. Epub 2011 
      May 25.