Asset Details
Do you wish to reserve the book?
Olig1/2 Orchestrates Progenitor Cell Fates during Mammalian Cortical Gliogenesis and Gliomagenesis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Olig1/2 Orchestrates Progenitor Cell Fates during Mammalian Cortical Gliogenesis and Gliomagenesis
Do you wish to request the book?
Olig1/2 Orchestrates Progenitor Cell Fates during Mammalian Cortical Gliogenesis and Gliomagenesis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Olig1/2 Orchestrates Progenitor Cell Fates during Mammalian Cortical Gliogenesis and Gliomagenesis
2025
Overview
During cortical gliogenesis, tri-potential intermediate progenitor cells (Tri-IPCs) differentiate into oligodendrocyte precursor cells (OPCs) or olfactory bulb interneuron intermediate progenitors (OBIN-IPCs) - a developmental program frequently co-opted in glioblastoma (GBM) to drive tumorigenesis. Here, we show that the transcription factors
Olig1/2
coordinately regulate Tri-IPC fate specification through dual transcriptional mechanisms: they activate OPC specification while simultaneously repressing OBIN-IPC generation by directly suppressing
Gsx2
expression. Genetic ablation of
Olig1/2
redirects Tri-IPCs from producing proliferative OPCs to generating non-proliferative OBIN-IPCs, concomitant with
Gsx2
upregulation. Mechanistically,
Olig1/2
bind and silence multiple conserved enhancer elements of
Gsx2
. Remarkably, in proneural GBM models,
Olig1/2
deletion reprograms glioma stem cells toward OBIN-IPC-like cells, potently inhibiting tumor growth and improving survival. Integrative multi-omics and immunohistochemical staining analyses further identify cortical Tri-IPCs as the likely cellular origin of human H3.3G34R/V gliomas. These findings establish
Olig1/2
as master regulators linking normal gliogenesis to gliomagenesis, and reveal therapeutic opportunities through fate reprogramming of glioma cells.
Developmental programs are frequently co-opted in glioblastoma. Here, the authors show the role of transcription factors Olig1/2 in fate specification of tri-potential intermediate progenitor cells and their connection with gliomagenesis in mouse models; they also show that Olig1/2 deletion can reprogram such stem cell differentiation and inhibit tumour growth.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/1
/ 38/39
/ Ablation
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - genetics
/ Basic Helix-Loop-Helix Transcription Factors - metabolism
/ Brain Neoplasms - metabolism
/ Deletion
/ Glioma
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Oligodendrocyte Precursor Cells - cytology
/ Oligodendrocyte Precursor Cells - metabolism
/ Oligodendrocyte Transcription Factor 2 - genetics
/ Oligodendrocyte Transcription Factor 2 - metabolism
/ Science
/ Tumors
