title: Region-specific Etv2 ablation revealed the critical origin of hemogenic capacity from Hox6-positive caudal-lateral primitive mesoderm.
abstract: Hematopoietic cells (HPCs) develop from hemogenic endothelial cells (ECs), a specialized type of ECs undergoing hematopoietic transition. However, the mesoderm origin for hemogenic ECs or HPCs has not been clarified. To examine the origin for hemogenic mesoderm, we inactivated Etv2, a master regulator for EC/HPC commitment, in specific regions. Region-specific Etv2 ablation in early mesoderm caused local EC differentiation block, resulting in the loss of specific vascular beds without compensatory migration of residual ECs into avascular area. This feature of local EC/HPC differentiation block was correlated to the hemogenic potential of each mesoderm subset. We found that caudal-lateral mesoderm of E7.5-8.5 embryos represent the pre-committed population critical for generating hemogenic ECs. Etv2 ablation in caudal-lateral mesoderm by Hoxb6 Cre or Hoxb6CreER transgene affected vitelline plexus formation and intra-aortic hematopoietic clusters. In differentiated embryonic stem cells, this mesoderm subset marked by Hoxb6-lateral mesoderm promoter showed enriched T lymphopoietic potential among Flk-1(+) cells, which could be regarded as a characteristic for definitive HPCs. These findings indicate that critical mesoderm precursors possibly for definitive type hemogenic ECs are regionally specified in primitive mesoderm, suggesting that Hoxb6(+) caudal-lateral mesoderm represents the critical source of HPCs, which are potentially useful to enrich definitive HPCs from embryonic stem cells.
authors: Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan. kataokah@cdb.riken.jp
authors: Hiroshi
authors: H
authors: Kataoka
authors: Misato
authors: M
authors: Hayashi
authors: Kumiko
authors: K
authors: Kobayashi
authors: Guo
authors: G
authors: Ding
authors: Yosuke
authors: Y
authors: Tanaka
authors: Shin-Ichi
authors: S
authors: Nishikawa
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006413:Hematopoietic System / Q000196:embryology*; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
chemical_list: C503994:ER71 protein, mouse; D018398:Homeodomain Proteins; C490537:Hoxb6 protein, mouse; D014157:Transcription Factors; D040301:Vascular Endothelial Growth Factor Receptor-2