Wnt9a Is Required for the Aortic Amplification of Nascent Hematopoietic Stem Cells

Cell Reports

卷:17

David Traver¹  Raquel Espín Palazón¹  Sara Wirth¹  Stephanie Grainger¹  Jenna Richter¹  Claire Pouget¹  Brianna Lonquich¹  Karl Willert¹  Matthew R. Swift²  Brant M. Weinstein³  Wiebke Herzog⁴  Kathrin Sabine Grassme⁴ 

[1] Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA;

[2] Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA;

[3] Section on Vertebrate Organogenesis, Division of Developmental Biology, NICHD, NIH, Bethesda, MD 20892, USA;

[4] University of Münster, 48149 Münster, Germany;

关键词: hematopoietic stem cells;    HSCs;    hematopoietic stem and progenitor cells;    HSPCs;    Wnt;    Wnt9a;    Myc;    proliferation;    aorta;   

DOI  :  10.1016/j.celrep.2016.10.027

来源: DOAJ

【 摘 要 】

All mature blood cell types in the adult animal arise from hematopoietic stem and progenitor cells (HSPCs). However, the developmental cues regulating HSPC ontogeny are incompletely understood. In particular, the details surrounding a requirement for Wnt/β-catenin signaling in the development of mature HSPCs are controversial and difficult to consolidate. Using zebrafish, we demonstrate that Wnt signaling is required to direct an amplification of HSPCs in the aorta. Wnt9a is specifically required for this process and cannot be replaced by Wnt9b or Wnt3a. This proliferative event occurs independently of initial HSPC fate specification, and the Wnt9a input is required prior to aorta formation. HSPC arterial amplification occurs prior to seeding of secondary hematopoietic tissues and proceeds, in part, through the cell cycle regulator myca (c-myc). Our results support a general paradigm, in which early signaling events, including Wnt, direct later HSPC developmental processes.

【 授权许可】

Unknown