Inhibition of Canonical Wnt Signaling Promotes Ex Vivo Maintenance and Proliferation of Hematopoietic Stem Cells in Zebrafish

• DOI: 10.1093/stmcls/sxac044
• Publication Date: 2022-06-27T22:07:06Z
• Authors: Koki Kimura; Shiori Yamamori; Masaharu Hazawa; Jingjing Kobayash...; Mao Kondo; Richard W Wong; Isao Kobayashi
• Keywords: Hematopoietic stem cell; RUNX1

Abstract The maintenance and proliferation of hematopoietic stem cells (HSCs) are tightly regulated by their niches in the bone marrow. analysis niche or stromal cell lines that can support HSCs has facilitated finding novel supporting factors for HSCs. Despite large efforts murine marrow; however, HSC expansion is still difficult ex vivo, highlighting need new approaches to elucidate molecular elements regulate zebrafish provides a unique model study as maintained kidney, allowing parallel view over evolution. Here, using line from kidney (ZKS), we uncover an inhibitor canonical Wnt signaling, IWR-1-endo, potent regulator Coculture assays revealed ZKS were part supportive maintenance, but not expansion, gata2a:GFP+runx1:mCherry+ (gata2a+runx1+) Transcriptome that, compared with candidate weakly expressed factor genes, thpo cxcl12, highly ligand wnt1, 7bb, 9a. Thpo supplementation culture slightly increased, inhibition signaling IWR-1-endo treatment largely increased number gata2a+runx1+ (>2-fold). Moreover, found be supplementing both without cells. Collectively, our data provide evidence used