Camilla U Niklasson1, Elina Fredlund1,2, Emanuela Monni3,4, Jessica M Lindvall5, Zaal Kokaia3,4, Emma U Hammarlund1, Marianne E Bronner6, Sofie Mohlin1,2,6. 1. Translational Cancer Research, Lund University Cancer Center at Medicon Village, Lund University, Lund, Sweden. 2. Division of Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden. 3. Laboratory of Stem Cells and Restorative Neurology, University Hospital, Lund, Sweden. 4. Lund Stem Cell Center, Lund University, Lund, Sweden. 5. National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. 6. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
Abstract
BACKGROUND: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development. RESULTS: Here, we show that HIF-2α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2α in vivo causes developmental delays, induces proliferation, and self-renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF-2α reveal enrichment of genes associated with cancer, invasion, epithelial-to-mesenchymal transition, and growth arrest. CONCLUSIONS: Taken together, these results suggest that expression levels of HIF-2α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.
BACKGROUND: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)-2α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development. RESULTS: Here, we show that HIF-2α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF-2α in vivo causes developmental delays, induces proliferation, and self-renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF-2α reveal enrichment of genes associated with cancer, invasion, epithelial-to-mesenchymal transition, and growth arrest. CONCLUSIONS: Taken together, these results suggest that expression levels of HIF-2α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development.
Authors: Camilla U Niklasson; Elina Fredlund; Emanuela Monni; Jessica M Lindvall; Zaal Kokaia; Emma U Hammarlund; Marianne E Bronner; Sofie Mohlin Journal: Dev Dyn Date: 2020-09-26 Impact factor: 3.780
Authors: Tammie Bishop; Denis Gallagher; Alberto Pascual; Craig A Lygate; Joseph P de Bono; Lynn G Nicholls; Patricia Ortega-Saenz; Henrik Oster; Bhathiya Wijeyekoon; Andrew I Sutherland; Alexandra Grosfeld; Julian Aragones; Martin Schneider; Katie van Geyte; Dania Teixeira; Antonio Diez-Juan; Jose Lopez-Barneo; Keith M Channon; Patrick H Maxwell; Christopher W Pugh; Alun M Davies; Peter Carmeliet; Peter J Ratcliffe Journal: Mol Cell Biol Date: 2008-03-10 Impact factor: 4.272
Authors: Camilla U Niklasson; Elina Fredlund; Emanuela Monni; Jessica M Lindvall; Zaal Kokaia; Emma U Hammarlund; Marianne E Bronner; Sofie Mohlin Journal: Dev Dyn Date: 2020-09-26 Impact factor: 3.780