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Gene Expression by array after Ferritin Knockdown in Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

ABSTRACT: Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE72203 | GEO | 2015/09/30

SECONDARY ACCESSION(S): PRJNA293351

REPOSITORIES: GEO

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Epigenetic Profile in Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

Project description:Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared to tissue-specific progenitors. Direct interrogation of iron uptake demonstrated CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin - two core iron regulators - to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, and on which CSCs have an epigenetically programmed, targetable dependence.

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Project description:Iron metabolism has emerged as a critical factor in cell viability, both in normal and pathological contexts. However, the intricate relationship between iron metabolism and the maintenance of adult stem cells and cancer stem cells remains incompletely understood. The ferritin complex, responsible for intracellular iron storage and buffering, plays a pivotal role in this process. Our research provides insights into the regulatory role of ferritin-mediated iron homeostasis in hematopoietic stem cells (HSCs).

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Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.

Project description: Not available

| S-EPMC4646058 | biostudies-literature

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Project description:This is a small model of ferritin iron sequestration kinetics. The model’s parameter values were determined from published kinetic and binding experiments and the model was validated against independent data not used in its construction. Beyond its utility to investigate properties of ferritin iron sequestration itself, we propose this model to be used as a building block for larger models of iron metabolism in a variety of specific cell types.

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