Autism risk genes converge on PBX1 to govern neural cell growth

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract The alteration of neural progenitor cell (NPC) proliferation underlies autism spectrum disorders (ASD). It remains unclear whether targeting convergent downstream targets among mutations from different genes and individuals can rescue this alteration. We identified PBX1 as a target three risk genes: CTNNB1 , PTEN DVL3 using isogenic iPSC-derived 2D NPCs. Overexpression the PBX1a isoform effectively rescued increased NPC in all ASD-related variants. Dysregulation NPCs was further confirmed publicly available datasets other models ASD. These findings spotlight known to play important roles during olfactory bulb/adult neurogenesis multiple cancers, an unexpected key target, influencing ASD neurodevelopmental syndromes.

Language: Английский

---

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

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 8, 2025

Neurodevelopmental disorders (NDDs) affect 4.7% of the global population and are associated with delays in brain development a spectrum impairments that can lead to lifelong disability even mortality. Identification biomarkers for accurate diagnosis medications effective treatment lacking, part due historical use preclinical model systems do not translate well clinic neurological disorders, such as rodents heterologous cell lines. Human-induced pluripotent stem cells (hiPSCs) promising vitro system modeling NDDs, providing opportunities understand mechanisms driving NDDs human neurons. Functional assays, including patch clamping, multielectrode array, imaging-based popular tools employed hiPSC disease models investigation. Recent progress machine learning (ML) algorithms also presents unprecedented advance NDD research process. In this review, we compare two-dimensional three-dimensional formats modeling, discuss applications functional offer insights on incorporating ML into hiPSC-based drug screening.

Language: Английский

---

Cerebellum structure; AMPA receptors; MAGEL2 gene

The Transmitter, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

---