Patterns of Wnt/Fzd/LRP gene expression during embryonic hematopoiesis

Corrigan, P.M., Dobbin, E., Freeburn, R.W. and Wheadon, H. (2009) Patterns of Wnt/Fzd/LRP gene expression during embryonic hematopoiesis. Stem Cells and Development, 18(5), pp. 759-771. (doi: 10.1089/scd.2008.0270)

Abstract

Wnt signaling plays several roles in hematopoiesis, promoting hemopoietic stem cell (HSC) self-renewal, providing proliferative signals for immature progenitors and regulating lineage commitment. To ascertain which Wnt proteins and receptors are important during hematopoietic development, we used two systems; in vitro hematopoietic differentiation of embryonic stem (ES) cells and tissues isolated from sites specifi c for hematopoiesis during mouse embryogenesis. Initially genes involved in hematopoiesis were profi led and indicate differentiating ES cells undergo a wave of primitive hematopoiesis (Day 3.75) similar to the mouse yolk sac, followed by a wave of more defi nitive hematopoiesis (Day 7.75) comparable to the aorta-gonad-mesonephros (AGM) and E15.5 liver with lineage commitment by Day 15. A similar biphasic expression pattern occurred for Wnt/Fzd/LRP genes with Wnt 3, 5a, 8a, Fzd4, and LRP5 becoming upregulated during primitive hematopoiesis, followed by Wnt3a, 6, 7b, 10b, and 16 during more defi nitive hematopoiesis. High expression of Wnt5a, Fzd4, and LRP5 during the fi rst phase of hematopoiesis suggests these genes are involved in early hematopoietic regulation. Wnt3a and 16 were also expressed at specifi c stages, with Wnt16 detected when the earliest lymphoid progenitors are formed (AGM and 2°BC of ES differentiation). Wnt3a expression corresponded with the induction of defi nitive hematopoiesis a period, which involves rapid expansion of HSC (Day 7.75 of ES differentiation, AGM and E15.5 liver). Supplementation with Wnt3a during ES hematopoietic differentiation increased proliferation and appeared to promote stem cell expansion. Overall this study provides valuable information on the Wnt/Fzd/LRP involved in supporting embryonic hematopoiesis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wheadon, Professor Helen
• Authors: Corrigan, P.M., Dobbin, E., Freeburn, R.W., and Wheadon, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Stem Cells and Development
• ISSN: 1547-3287