Overlapping requirements for Tet2 and Tet3 in normal development and hematopoietic stem cell emergence Journal Article

Authors: Li, C.; Lan, Y.; Schwartz-Orbach, L.; Korol, E.; Tahiliani, M.; Evans, T.; Goll, M. G.
Article Title: Overlapping requirements for Tet2 and Tet3 in normal development and hematopoietic stem cell emergence
Abstract: 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. © 2015 The Authors.
Keywords: signal transduction; adult; controlled study; unclassified drug; gene mutation; nonhuman; animal tissue; gene; gene expression; embryo; animal experiment; genotype; notch receptor; embryo development; genetic transcription; brain development; hematopoiesis; hematopoietic stem cell; endothelium; zebra fish; mutant; larva; protein tet2; orthology; 5 methylcytosine; protein tet3; dioxygenase; scl gene; priority journal; article; runx1 gene; gata2b gene
Journal Title: Cell Reports
Volume: 12
Issue: 7
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2015-08-18
Start Page: 1133
End Page: 1143
Language: English
DOI: 10.1016/j.celrep.2015.07.025
PROVIDER: scopus
PMCID: PMC4545447
PUBMED: 26257178
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Mary Grace Goll
    6 Goll
  2. Chen Li
    6 Li