Back

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

Mohlin, S.; Persson, C. U.; Fredlund, E.; Monni, E.; Lindvall, J. M.; Kokaia, Z.; Hammarlund, E.; Bronner, M. E.

2020-01-23 developmental biology
10.1101/2020.01.22.915199 bioRxiv
Show 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)-2 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-2 is expressed in trunk neural crest cells of human, murine and avian embryos. Modulating HIF-2 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-2 reflect the in vivo phenotype. The results suggest that expression levels of HIF-2 must be strictly controlled and abnormal levels increase stemness and may promote metastasis. Our findings help elucidate the role of HIF-2 during normal development with implications also in tumor initiation at the onset of neuroblastoma.

Matching journals

The top 2 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.