PMID- 24598081
OWN - NLM
STAT- MEDLINE
DCOM- 20150102
LR  - 20211021
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 7
DP  - 2014 Mar 5
TI  - Pten regulates homeostasis and inflammation-induced migration of myelocytes in 
      zebrafish.
PG  - 17
LID - 10.1186/1756-8722-7-17 [doi]
AB  - BACKGROUND: Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) is 
      frequently observed in hematopoietic malignancies. Although PTEN has been 
      implicated in maintaining the quiescence of hematopoietic stem cells (HSCs), its 
      role in hematopoiesis during ontogeny remains largely unexplored. METHODS: The 
      expression of hematopoietic marker genes was analyzed via whole mount in situ 
      hybridization assay in ptena and ptenb double mutant zebrafish. The embryonic 
      myelopoiesis was characterized by living imaging and whole mount in situ 
      immunofluorescence with confocal microscopy, as well as cell-specific chemical 
      staining for neutrophils and macrophages. Analyses of the involved signaling 
      pathway were carried out by inhibitor treatment and mRNA injection. RESULTS: 
      Pten-deficient zebrafish embryos exhibited a strikingly increased number of 
      myeloid cells, which were further characterized as being immune deficient. In 
      accordance with this finding, the inhibition of phosphoinositide 3-kinase (PI3K) 
      or the mechanistic target of rapamycin (mTOR) corrected the expansive 
      myelopoiesis in the pten-deficient embryos. Further mechanistic studies revealed 
      that the expression of cebpa, a critical transcription factor in myeloid 
      precursor cells, was downregulated in the pten-deficient myeloid cells, whereas 
      the injection of cebpa mRNA markedly ameliorated the dysmyelopoiesis induced by 
      the loss of pten. CONCLUSIONS: Our data provide in vivo evidence that definitive 
      myelopoiesis in zebrafish is critically regulated by pten via the elevation of 
      cebpa expression.
FAU - Dong, Zhi-Wei
AU  - Dong ZW
FAU - Ren, Chun-Guang
AU  - Ren CG
FAU - Xia, Yu
AU  - Xia Y
FAU - Su, Dan
AU  - Su D
FAU - Du, Ting-Ting
AU  - Du TT
FAU - Fan, Hong-Bo
AU  - Fan HB
FAU - Yuan, Hao
AU  - Yuan H
FAU - Wang, Lei
AU  - Wang L
FAU - Dong, Mei
AU  - Dong M
FAU - Li, Wei-Chun
AU  - Li WC
FAU - Jin, Yi
AU  - Jin Y
FAU - Chen, Yi
AU  - Chen Y
FAU - Deng, Min
AU  - Deng M
FAU - Liu, Ting-Xi
AU  - Liu TX
FAU - Gu, Ai-Hua
AU  - Gu AH
AD  - Key Laboratory of Stem Cell Biology, State Key Laboratory for Medical Genomics 
      and Laboratory of Development and Diseases, Institute of Health Sciences, 
      Shanghai Institutes for Biological Sciences, Graduate School of the Chinese 
      Academy of Sciences, Shanghai 200025, China. aihuagu@njmu.edu.cn.
FAU - Zhou, Yong
AU  - Zhou Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140305
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Growth Processes/physiology
MH  - Cell Movement/*physiology
MH  - Homeostasis
MH  - Inflammation/*metabolism
MH  - Myeloid Cells/*cytology/*metabolism
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Zebrafish
PMC - PMC4015859
EDAT- 2014/03/07 06:00
MHDA- 2015/01/03 06:00
PMCR- 2014/03/05
CRDT- 2014/03/07 06:00
PHST- 2014/02/02 00:00 [received]
PHST- 2014/02/27 00:00 [accepted]
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/01/03 06:00 [medline]
PHST- 2014/03/05 00:00 [pmc-release]
AID - 1756-8722-7-17 [pii]
AID - 10.1186/1756-8722-7-17 [doi]
PST - epublish
SO  - J Hematol Oncol. 2014 Mar 5;7:17. doi: 10.1186/1756-8722-7-17.