Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells
(2021) In Developmental Dynamics 250(2). p.191-236- 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... (More)
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.
(Less)
- author
- Niklasson, Camilla U. LU ; Fredlund, Elina LU ; Monni, Emanuela LU ; Lindvall, Jessica M. ; Kokaia, Zaal LU ; Hammarlund, Emma U. LU ; Bronner, Marianne E. and Mohlin, Sofie LU
- organization
-
- LUCC: Lund University Cancer Centre
- Division of Translational Cancer Research
- Stem Cells & Restorative Neurology (research group)
- Neural stem cell biology and therapy (research group)
- Neurology, Lund
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Stem Cell Center
- EpiHealth: Epidemiology for Health
- Childhood Cancer Research Unit (research group)
- Paediatrics (Lund)
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- embryogenesis, HIF-2α, migration, neural crest, stem cells, trunk neural crest
- in
- Developmental Dynamics
- volume
- 250
- issue
- 2
- pages
- 191 - 236
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:32940375
- scopus:85091426123
- ISSN
- 1058-8388
- DOI
- 10.1002/dvdy.253
- language
- English
- LU publication?
- yes
- id
- 7c2b8dff-966d-468c-868d-55bbe6462e50
- date added to LUP
- 2020-10-28 08:14:13
- date last changed
- 2024-11-14 15:23:29
@article{7c2b8dff-966d-468c-868d-55bbe6462e50, abstract = {{<p>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.</p>}}, author = {{Niklasson, Camilla U. and Fredlund, Elina and Monni, Emanuela and Lindvall, Jessica M. and Kokaia, Zaal and Hammarlund, Emma U. and Bronner, Marianne E. and Mohlin, Sofie}}, issn = {{1058-8388}}, keywords = {{embryogenesis; HIF-2α; migration; neural crest; stem cells; trunk neural crest}}, language = {{eng}}, number = {{2}}, pages = {{191--236}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Developmental Dynamics}}, title = {{Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells}}, url = {{http://dx.doi.org/10.1002/dvdy.253}}, doi = {{10.1002/dvdy.253}}, volume = {{250}}, year = {{2021}}, }