Interplay of pu.1 and gata1 determines myelo-erythroid progenitor cell fate in zebrafish.
The zebrafish is a powerful model system for investigating embryonic vertebrate hematopoiesis, allowing for the critical in vivo analysis of cell lineage determination. In this study, we identify zebrafish myeloerythroid progenitor cells (MPCs) that are likely to represent the functional equivalent of mammalian common myeloid progenitors. Utilizing transgenic pu.1-GFP fish, real-time MPC differentiation was correlated with dynamic changes in cell motility, morphology, and gene expression. Unlike mammalian hematopoiesis, embryonic zebrafish myelopoiesis and erythropoiesis occur in anatomically separate locations. Gene knockdown experiments and transplantation assays demonstrated the reciprocal negative regulation of pu.1 and gata1 and their non-cell-autonomous regulation that determines myeloid versus erythroid MPC fate in the distinct blood-forming regions. Furthermore, forced expression of pu.1 in the bloodless mutant cloche resulted in myelopoietic rescue, providing intriguing evidence that this gene can function in the absence of some stem cell genes, such as scl, in governing myelopoiesis.
Rhodes
Jennifer
J
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Hagen
Andreas
A
Hsu
Karl
K
Deng
Min
M
Liu
Ting Xi
TX
Look
A Thomas
AT
Kanki
John P
JP
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004627:Embryonic Induction; D015672:Erythroid Precursor Cells / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D005434:Flow Cytometry / Q000379:methods; D050982:GATA1 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D017403:In Situ Hybridization / Q000379:methods; D008845:Microinjections / Q000379:methods; D008954:Models, Biological; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014180:Transplantation / Q000379:methods; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D049452:Green Fluorescent Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000099232:Proto-Oncogene Protein Spi-1; C494691:gata1a protein, zebrafish