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Cancer-associated HIF-2α impacts trunk neural crest stemness

Mohlin, Sofie and Persson, Camilla U. and Fredlund, Elina and Monni, Emanuela and Lindvall, Jessica M. and Kokaia, Zaal and Hammarlund, Emma and Bronner, Marianne E. (2020) Cancer-associated HIF-2α impacts trunk neural crest stemness. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200123-094934019

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Abstract

The neural crest is a stem cell population that gives rise to sympathetic ganglia, the cell type of origin of neuroblastoma. Hypoxia Inducible Factor (HIF)-2α is associated with high risk neuroblastoma, however, little is known about its role in normal neural crest development. To address this important question, here we show that HIF-2α is expressed in trunk neural crest cells of human, murine and avian embryos. Modulating HIF-2α in vivo not only causes developmental delays but also induces proliferation and stemness of neural crest cells while altering the number of cells migrating ventrally to sympathoadrenal sites. Transcriptome changes after loss of HIF-2α reflect the in vivo phenotype. The results suggest that expression levels of HIF-2α must be strictly controlled and abnormal levels increase stemness and may promote metastasis. Our findings help elucidate the role of HIF-2α during normal development with implications also in tumor initiation at the onset of neuroblastoma.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.01.22.915199DOIDiscussion Paper
ORCID:
AuthorORCID
Mohlin, Sofie0000-0002-2458-3963
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online Jan. 23, 2020. We would like to thank Erica Hutchins, Shashank Gandhi and Siv Beckman for skillful technical assistance and Anni Glud and Ronnie N. Glud for providing microsensor technique and expertise. This work was supported by the Swedish Cancer Society, the Swedish Childhood Cancer Fund, the Craaford Foundation, Jeansson Foundations, Ollie and Elof Ericsson’s foundation, the Mary Bevé Foundation, Magnus Bergvall’s foundation, the Thelma Zoega foundation for medical research, Hans von Kantzow’s foundation, the Royal Physiographic Society of Lund, the Gyllenstierna Krapperup’s Foundation, and Gunnar Nilssons Cancerstiftelse (to SM), DE027568 and R01HL14058 (to MEB). We thank Center for Translational Genomics, Lund University and Clinical Genomics Lund, SciLifeLab for providing sequencing service. Support by NBIS (National Bioinformatics Infrastructure Sweden) is gratefully acknowledged. Author contributions: SM, CUP, EF and EH performed experiments. SM, EH and MEB analyzed data. SM and JML analyzed RNA sequencing data. EM and ZK provided materials. SM and MEB supervised the study. SM wrote the original draft of the manuscript while all authors reviewed and edited the manuscript. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Swedish Cancer SocietyUNSPECIFIED
Swedish Childhood Cancer FundUNSPECIFIED
Craaford FoundationUNSPECIFIED
Jeansson FoundationsUNSPECIFIED
Ollie and Elof Ericssons FoundationUNSPECIFIED
Mary Bevé FoundationUNSPECIFIED
Magnus Bergvall FoundationUNSPECIFIED
Thelma Zoéga FoundationUNSPECIFIED
Hans von Kantzow’s FoundationUNSPECIFIED
Royal Physiographic Society of LundUNSPECIFIED
Gyllenstierna Krapperup’s FoundationUNSPECIFIED
Gunnar Nilsson Cancer FoundationUNSPECIFIED
NIHDE027568
NIHR01HL14058
National Bioinformatics Infrastructure SwedenUNSPECIFIED
Subject Keywords:Neural crest, trunk neural crest, neuroblastoma, hypoxia inducible factor-2, HIF, chick embryo
Record Number:CaltechAUTHORS:20200123-094934019
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200123-094934019
Official Citation:Cancer-associated HIF-2α impacts trunk neural crest stemness. Sofie Mohlin, Camilla U Persson, Elina Fredlund, Emanuela Monni, Jessica M Lindvall, Zaal Kokaia, Emma Hammarlund, Marianne E Bronner. bioRxiv 2020.01.22.915199; doi: https://doi.org/10.1101/2020.01.22.915199
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100869
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Jan 2020 18:48
Last Modified:23 Jan 2020 18:48

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