GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile

Patricia Rusu, Chunxuan Shao, Anna Neuerburg, Azer Aylin Acikgoz, Yonghe Wu, Peng Zou, Prasad Phapale, Tchirupura S. Shankar, Kristina Doring, Steffen Dettling, Huiqin Korkel-Qu, Gozde Bekki, Barbara Costa, Te Guo, Olga Friesen, Magdalena Schlotter, Mathias Heikenwalder, Darjus F. Tschaharganeh, Bernd Bukau, Günter KramerPeter Angel, Christel Herold-Mende, Bernhard Radlwimmer, Hai-Kun Liu

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Brain tumor stem cells (BTSCs) are a chemoresistant population that can drive tumor growth and relapse, but the lack of BTSC-specific markers prevents selective targeting that spares resident stem cells. Through a ribosome-profiling analysis of mouse neural stem cells (NSCs) and BTSCs, we find glycerol-3-phosphate dehydrogenase 1 (GPD1) expression specifically in BTSCs and not in NSCs. GPD1 expression is present in the dormant BTSC population, which is enriched at tumor borders and drives tumor relapse after chemotherapy. GPD1 inhibition prolongs survival in mouse models of glioblastoma in part through altering cellular metabolism and protein translation, compromising BTSC maintenance. Metabolomic and lipidomic analyses confirm that GPD1+ BTSCs have a profile distinct from that of NSCs, which is dependent on GPD1 expression. Similar GPD1 expression patterns and prognostic associations are observed in human gliomas. This study provides an attractive therapeutic target for treating brain tumors and new insights into mechanisms regulating BTSC dormancy. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their normal tissue-resident counterparts. Rusu et al. identify GPD1 as a specific marker for dormant and chemoresistant BTSCs and show that targeting GPD1 disrupts BTSC maintenance and extends survival.

Original languageEnglish
Pages (from-to)241-257
Number of pages17
JournalCell Stem Cell
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Aug 2019
Externally publishedYes

Keywords

  • cancer stem cell
  • dormancy
  • glioblastoma
  • glycerol-3-phosphate dehydrogenase 1
  • mouse model
  • ribosome profiling

Cite this

Rusu, P., Shao, C., Neuerburg, A., Acikgoz, A. A., Wu, Y., Zou, P., Phapale, P., Shankar, T. S., Doring, K., Dettling, S., Korkel-Qu, H., Bekki, G., Costa, B., Guo, T., Friesen, O., Schlotter, M., Heikenwalder, M., Tschaharganeh, D. F., Bukau, B., ... Liu, H-K. (2019). GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile. Cell Stem Cell, 25(2), 241-257. https://doi.org/10.1016/j.stem.2019.06.004