# BRD1 haploinsufficiency alters early neuronal programming and disrupts maturation in human induced glutamatergic neurons

## TL;DR

This study shows that reduced BRD1 levels disrupt early human neuron development and maturation, leading to altered neurodevelopmental processes and synaptic function.

## Contribution

The study reveals that BRD1 haploinsufficiency accelerates neuronal maturation and alters synapse formation in human glutamatergic neurons.

## Key findings

- BRD1 haploinsufficiency causes accelerated maturation and altered neurodevelopmental trajectories in human induced glutamatergic neurons.
- BRD1+/− neurons show downregulation of pluripotency markers and upregulation of synapse-related genes like GRIA3.
- Despite early maturation signs, BRD1+/− neurons form smaller synapses and exhibit increased neuronal activity.

## Abstract

BRD1 is an epigenetic regulator implicated in neurodevelopmental and psychiatric disorders, yet its role in human neuronal differentiation, maturation, and function remains poorly understood. Here we show that BRD1 haploinsufficiency disrupts early neuronal programming, resulting in accelerated maturation and altered neurodevelopmental trajectories in human induced glutamatergic neurons. Transcriptomic profiling reveals an early shift toward neuronal identity, characterized by downregulation of pluripotency markers and persistent upregulation of genes involved in synapse assembly and organization, including GRIA3. Despite this, BRD1+/− neurons form significantly smaller synapses and display increased neuronal activity. Our findings highlight BRD1 as a key regulator of neurodevelopmental timing and synaptic maturation, and network activity reinforcing growing evidence that disruptions in chromatin-mediated control of differentiation and synaptic organization contribute to neurodevelopmental disorders.