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ZFIN ID: ZDB-PUB-150811-3
Overlapping Requirements for Tet2 and Tet3 in Normal Development and Hematopoietic Stem Cell Emergence
Li, C., Lan, Y., Schwartz-Orbach, L., Korol, E., Tahiliani, M., Evans, T., Goll, M.G.
Date: 2015
Source: Cell Reports 12(7): 1133-43 (Journal)
Registered Authors: Evans, Todd, Goll, Mary
Keywords: none
MeSH Terms:
  • Animals
  • Dioxygenases/genetics
  • Dioxygenases/metabolism*
  • Embryonic Development
  • Endothelial Progenitor Cells/cytology
  • Endothelial Progenitor Cells/metabolism
  • Gene Expression Regulation, Developmental
  • Hematopoiesis*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Receptors, Notch/metabolism
  • Signal Transduction
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 26257178 Full text @ Cell Rep.
The Tet family of methylcytosine dioxygenases (Tet1, Tet2, and Tet3) convert 5-methylcytosine to 5-hydroxymethylcytosine. To date, functional overlap among Tet family members has not been examined systematically in the context of embryonic development. To clarify the potential for overlap among Tet enzymes during development, we mutated the zebrafish orthologs of Tet1, Tet2, and Tet3 and examined single-, double-, and triple-mutant genotypes. Here, we identify Tet2 and Tet3 as the major 5-methylcytosine dioxygenases in the zebrafish embryo and uncover a combined requirement for Tet2 and Tet3 in hematopoietic stem cell (HSC) emergence. We demonstrate that Notch signaling in the hemogenic endothelium is regulated by Tet2/3 prior to HSC emergence and show that restoring expression of the downstream gata2b/scl/runx1 transcriptional network can rescue HSCs in tet2/3 double mutant larvae. Our results reveal essential, overlapping functions for tet genes during embryonic development and uncover a requirement for 5hmC in regulating HSC production.