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Related Experiment Video

Updated: Sep 18, 2025

Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein

Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein

Published on: June 6, 2025

Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger

Bharath Kumar Reddy¹, Nikhita Annaiyappa², Aditi Bhattacharya²

¹Centre for High Impact Neuroscience and Translational Applications, TCG Centres for Research and Education in Science and Technology; Academy of Scientific and Innovative Research (AcSIR).

Journal of Visualized Experiments : Jove

|June 23, 2025

Summary

Fragile X syndrome (FXS) astrocytes exhibit metabolic dysregulation. This study developed a human stem cell model to investigate FXS-associated astrocytic dysfunction in neurodevelopmental disorders.

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Isolation and Direct Neuronal Reprogramming of Mouse Astrocytes

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Last Updated: Sep 18, 2025

Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein

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Published on: June 6, 2025

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Isolation and Direct Neuronal Reprogramming of Mouse Astrocytes

Isolation and Direct Neuronal Reprogramming of Mouse Astrocytes

Published on: July 7, 2022

Area of Science:

Neuroscience
Stem Cell Biology
Developmental Biology

Background:

Fragile X syndrome (FXS) is a primary inherited cause of autism spectrum disorder and intellectual disability.
Previous FXS research predominantly used rodent models and focused on neurons, neglecting glial cell roles.
Understanding astrocyte involvement in FXS is crucial for a comprehensive view of neurodevelopmental disorders.

Purpose of the Study:

To develop a human stem cell-based model for studying astrocyte development and function in FXS.
To investigate the impact of FXS on human astrocyte maturation and metabolism.
To establish a framework for exploring cell-autonomous and non-cell-autonomous effects in FXS-related neurodevelopmental disorders.

Main Methods:

Human induced pluripotent stem cells were patterned into neuroectoderm using SMAD inhibition and small molecules.
Astrocytic progenitor cells (APCs) were generated from control and FXS patient-derived stem cells.
APCs were differentiated into forebrain astrocytes using ciliary neurotrophic factor, and their metabolic functions were assessed.

Main Results:

A protocol was established to generate functional human astrocytes from stem cells, capturing key developmental and gliogenesis milestones.
FXS patient-derived astrocytes demonstrated dysregulated glycolytic and mitochondrial metabolism compared to controls.
The generated astrocytes showed functional calcium responses to ATP, confirming their viability.

Conclusions:

This study presents a novel human stem cell-derived model for investigating astrocytic contributions to FXS.
The findings highlight metabolic abnormalities in FXS astrocytes, suggesting a role in the disorder's pathophysiology.
The developed model serves as a valuable platform for future research into neurodevelopmental disorders affecting glial function.