Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders

Neurodevelopmental disorders (NDDs) affect 4.7% of the global population and are associated with delays in brain development and a spectrum of impairments that can lead to lifelong disability and even mortality. Identification of biomarkers for accurate diagnosis and medications for effective treatm...

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Main Authors: Ziqin Yang, Nicole A. Teaney, Elizabeth D. Buttermore, Mustafa Sahin, Wardiya Afshar-Saber
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2024.1524577/full
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author Ziqin Yang
Ziqin Yang
Nicole A. Teaney
Nicole A. Teaney
Elizabeth D. Buttermore
Elizabeth D. Buttermore
Elizabeth D. Buttermore
Mustafa Sahin
Mustafa Sahin
Mustafa Sahin
Wardiya Afshar-Saber
Wardiya Afshar-Saber
author_facet Ziqin Yang
Ziqin Yang
Nicole A. Teaney
Nicole A. Teaney
Elizabeth D. Buttermore
Elizabeth D. Buttermore
Elizabeth D. Buttermore
Mustafa Sahin
Mustafa Sahin
Mustafa Sahin
Wardiya Afshar-Saber
Wardiya Afshar-Saber
author_sort Ziqin Yang
collection DOAJ
description Neurodevelopmental disorders (NDDs) affect 4.7% of the global population and are associated with delays in brain development and a spectrum of impairments that can lead to lifelong disability and even mortality. Identification of biomarkers for accurate diagnosis and medications for effective treatment are lacking, in part due to the historical use of preclinical model systems that do not translate well to the clinic for neurological disorders, such as rodents and heterologous cell lines. Human-induced pluripotent stem cells (hiPSCs) are a promising in vitro system for modeling NDDs, providing opportunities to understand mechanisms driving NDDs in human neurons. Functional assays, including patch clamping, multielectrode array, and imaging-based assays, are popular tools employed with hiPSC disease models for disease investigation. Recent progress in machine learning (ML) algorithms also presents unprecedented opportunities to advance the NDD research process. In this review, we compare two-dimensional and three-dimensional hiPSC formats for disease modeling, discuss the applications of functional assays, and offer insights on incorporating ML into hiPSC-based NDD research and drug screening.
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spelling doaj-art-16780215b11a4791a15c6bac7f21eea72025-01-08T06:11:47ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-01-011810.3389/fnins.2024.15245771524577Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disordersZiqin Yang0Ziqin Yang1Nicole A. Teaney2Nicole A. Teaney3Elizabeth D. Buttermore4Elizabeth D. Buttermore5Elizabeth D. Buttermore6Mustafa Sahin7Mustafa Sahin8Mustafa Sahin9Wardiya Afshar-Saber10Wardiya Afshar-Saber11Rosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesFM Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesRosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesFM Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesRosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesFM Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesHuman Neuron Core, Boston Children’s Hospital, Boston, MA, United StatesRosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesFM Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesHuman Neuron Core, Boston Children’s Hospital, Boston, MA, United StatesRosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesFM Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United StatesNeurodevelopmental disorders (NDDs) affect 4.7% of the global population and are associated with delays in brain development and a spectrum of impairments that can lead to lifelong disability and even mortality. Identification of biomarkers for accurate diagnosis and medications for effective treatment are lacking, in part due to the historical use of preclinical model systems that do not translate well to the clinic for neurological disorders, such as rodents and heterologous cell lines. Human-induced pluripotent stem cells (hiPSCs) are a promising in vitro system for modeling NDDs, providing opportunities to understand mechanisms driving NDDs in human neurons. Functional assays, including patch clamping, multielectrode array, and imaging-based assays, are popular tools employed with hiPSC disease models for disease investigation. Recent progress in machine learning (ML) algorithms also presents unprecedented opportunities to advance the NDD research process. In this review, we compare two-dimensional and three-dimensional hiPSC formats for disease modeling, discuss the applications of functional assays, and offer insights on incorporating ML into hiPSC-based NDD research and drug screening.https://www.frontiersin.org/articles/10.3389/fnins.2024.1524577/fullhiPSCneurodevelopmental disorderspatch clampingMEAvoltage imagingcalcium imaging
spellingShingle Ziqin Yang
Ziqin Yang
Nicole A. Teaney
Nicole A. Teaney
Elizabeth D. Buttermore
Elizabeth D. Buttermore
Elizabeth D. Buttermore
Mustafa Sahin
Mustafa Sahin
Mustafa Sahin
Wardiya Afshar-Saber
Wardiya Afshar-Saber
Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders
Frontiers in Neuroscience
hiPSC
neurodevelopmental disorders
patch clamping
MEA
voltage imaging
calcium imaging
title Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders
title_full Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders
title_fullStr Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders
title_full_unstemmed Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders
title_short Harnessing the potential of human induced pluripotent stem cells, functional assays and machine learning for neurodevelopmental disorders
title_sort harnessing the potential of human induced pluripotent stem cells functional assays and machine learning for neurodevelopmental disorders
topic hiPSC
neurodevelopmental disorders
patch clamping
MEA
voltage imaging
calcium imaging
url https://www.frontiersin.org/articles/10.3389/fnins.2024.1524577/full
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