The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells.
Hematopoietic development is closely linked to that of blood vessels and the two processes are regulated in large part by transcription factors that control cell fate decisions and cellular differentiation. Both blood and blood vessels derive from a common progenitor, termed the hemangioblast, but the factor(s) specifying the development and differentiation of this stem cell population into the hematopoietic and vascular lineages remain ill defined. Here, we report that knockdown of the Krüppel-like transcription factor ZBP-89 in zebrafish embryos results in a bloodless phenotype, caused by disruption of both primitive and definitive hematopoiesis, while leaving primary blood vessel formation intact. Injection of ZBP-89 mRNA into cloche zebrafish embryos, which lack both the hematopoietic and endothelial lineages, rescues hematopoiesis but not vasculogenesis. Injection of mRNA for Stem Cell Leukemia (SCL), a transcription factor that directs hemangioblast development into blood cell precursors, rescues the bloodless phenotype in ZBP-89 zebrafish morphants. Forced expression of ZBP-89 induces the expansion of hematopoietic progenitors in wild-type zebrafish and in mouse embryonic stem cell cultures but inhibits angiogenesis in vivo and in vitro. These findings establish a unique regulatory role for ZBP-89, positioned at the interface between early blood and blood vessel development.
Li
Xiangen
X
Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Xiong
Jing-Wei
JW
Shelley
C Simon
CS
Park
Heiyoung
H
Arnaout
M Amin
MA
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D009154:Mutation / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C491741:Zfp148 protein, mouse; C528125:znf148 protein, zebrafish