Cpsf1 is required for definitive HSC survival in zebrafish

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Blood (Impact Factor: 10.45). 02/2011; 117(15):3996-4007. DOI: 10.1182/blood-2010-08-304030
Source: PubMed

ABSTRACT A comprehensive understanding of the genes and pathways regulating hematopoiesis is needed to identify genes causally related to bone marrow failure syndromes, myelodysplastic syndromes, and hematopoietic neoplasms. To identify novel genes involved in hematopoiesis, we performed an ethyl-nitrosourea mutagenesis screen in zebrafish (Danio rerio) to search for mutants with defective definitive hematopoiesis. We report the recovery and analysis of the grechetto mutant, which harbors an inactivating mutation in cleavage and polyadenylation specificity factor 1 (cpsf1), a gene ubiquitously expressed and required for 3' untranslated region processing of a subset of pre-mRNAs. grechetto mutants undergo normal primitive hematopoiesis and specify appropriate numbers of definitive HSCs at 36 hours postfertilization. However, when HSCs migrate to the caudal hematopoietic tissue at 3 days postfertilization, their numbers start decreasing as a result of apoptotic cell death. Consistent with Cpsf1 function, c-myb:EGFP(+) cells in grechetto mutants also show defective polyadenylation of snrnp70, a gene required for HSC development. By 5 days postfertilization, definitive hematopoiesis is compromised and severely decreased blood cell numbers are observed across the myeloid, erythroid, and lymphoid cell lineages. These studies show that cpsf1 is essential for HSC survival and differentiation in caudal hematopoietic tissue.

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    Developmental Cell 05/2014; 29(3):350-9. DOI:10.1016/j.devcel.2014.04.003 · 9.71 Impact Factor
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    • "Thus, the VDA, CHT and kidney of the zebrafish are respectively the functional analogs of the AGM, liver and bone marrow in mice (Chen and Zon, 2009). Using forward genetic analyses, three previously uncharacterized factors [rumba (znf574), haus3 and cpsf1] have recently been found to play an essential role in regulating fetal hematopoiesis in zebrafish (Bolli et al., 2011; Du et al., 2011), confirming that the employment of an unbiased forward genetic approach in zebrafish can complement our current knowledge of mammals. Sumoylation is a post-translational modification that participates in various cellular processes, such as regulation of gene transcription, the cell cycle, genomic integrity, stress responses and organogenesis (Hay, 2005). "
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    Development 12/2012; 139(23):4321-9. DOI:10.1242/dev.081869 · 6.46 Impact Factor
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    • "These cells go on to populate the adult organs of haematopoiesis in the zebrafish, the kidney and the thymus. The precise timing of the move from primitive wave haematopoiesis to definitive wave haematopoiesis has yet to be fully established, but evidence from globin gene expression and mutants with normal primitive wave blood production suggests that the major contribution of haematopoiesis comes from definitive HSC derived cells by around 5 days post fertilization [12] [13] [14] "
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    Advances in Hematology 07/2012; 2012:358518. DOI:10.1155/2012/358518
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