Biology subjects

Huang, Y.-M.

Publications and source records attributed to Huang, Y.-M..

4 recordsLinked to original sources

bioRxiv2026

A Distinct Layer 1 Astrocyte Program Shapes Perisynaptic Structure and Calcium Signaling in Mouse Motor Cortex

Although layer-specific molecular and morphological diversity among cortical astrocytes is increasingly well established, how these distinct states are linked to specialized calcium signaling and maintained in the adult cortex remains unclear. Here, combining super-resolution structural imaging, two-photon calcium imaging, and analysis of public single-cell and spatial transcriptomic resources, we identify Layer 1 (L1) astrocytes in mouse primary motor cortex as a distinct superficial astrocyte program. These cells occupy compact territories yet contain dense synapse-associated loop-like structures and display frequent, fast, broadly spreading calcium events that engage a large fraction of the territory. Transcriptomic analyses identify Id1 and Id3 as enriched components of this superficial program. CRISPR-Cas9 deletion of Id1 and Id3 in adult astrocytes selectively disrupts L1 and superficial Layer 2/3 (L2/3) astrocytes, expanding territory size, reducing fine-process complexity, and suppressing calcium activity. Thus, adult layer-specific transcriptional programs maintain specialized astrocyte structure and signaling. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/712002v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@89c916org.highwire.dtl.DTLVardef@1f0d71eorg.highwire.dtl.DTLVardef@bb02f3org.highwire.dtl.DTLVardef@1bedf7e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LILayer 1 astrocytes in mouse motor cortex have compact, loop-rich nanoarchitecture C_LIO_LILayer 1 astrocytes show fast, frequent, widespread calcium events C_LIO_LISingle-cell data define a superficial astrocyte state enriched for Id1 and Id3 C_LIO_LIAdult Id1/Id3 loss selectively disrupts Layer 1 astrocyte structure and calcium C_LI In BriefBhattacharjee et al., identify a specialized Layer 1 astrocyte state in mouse motor cortex, defined by compact, loop-rich nanoarchitecture and unusually high calcium signaling. Id1/Id3 deletion selectively disrupts this superficial program, linking layer-specific astrocyte form and function to adult transcriptional control.

neuroscience↗

bioRxiv2025

Rescuing Neurodevelopmental Deficits in AMPA Receptor Gain-of-Function Mutant

AMPA receptors (AMPARs) mediate fast excitatory synaptic transmission and are essential for neuronal development and brain function. We investigated the role of a recurrent variant in the AMPAR GluA1 subunit (GRIA1 p.A636T) identified in individuals with autism spectrum disorder (ASD) and intellectual disability (ID). To test causality and mechanism, we generated a Gria1-A636T knock-in mouse model. Mutant mice exhibited core ASD/ID-like behaviors and a selective hippocampal vulnerability characterized by progressive dendritic atrophy and neuronal loss. Despite reduced GluA1-containing complexes, AMPARs displayed synaptic hyperexcitability and failed to undergo the normal postnatal transition to calcium-impermeable AMPARs, resulting in persistent excitotoxicity. To explore therapeutic intervention, we designed an allele-specific antisense oligonucleotide to specifically silence the mutant transcript. A single neonatal administration of the antisense oligonucleotide entirely prevented hippocampal pathology and ameliorated behavioral deficits. These findings establish GRIA1-A636T as a gain-of-function mutation that drives developmental excitotoxicity and highlight the potential of RNA-targeted precision medicine for neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

Underwater CAM photosynthesis elucidated by Isoetes genome

To conserve water in arid environments, numerous plant lineages have independently evolved Crassulacean Acid Metabolism (CAM). Interestingly, Isoetes, an aquatic lycophyte, can also perform CAM as an adaptation to low CO2 availability underwater. However, little is known about the evolution of CAM in aquatic plants and the lack of genomic data has hindered comparison between aquatic and terrestrial CAM. Here, we investigated the underwater CAM in Isoetes taiwanensis by generating a high-quality genome assembly and RNA-seq time course. Despite broad similarities between CAM in Isoetes and terrestrial angiosperms, we identified several key differences. Notably, for carboxylation of PEP, Isoetes recruited the lesser-known "bacterial-type" PEPC, along with the "plant-type" exclusively used in other terrestrial CAM and C4 plants. Furthermore, we found that circadian control of key CAM pathway genes has diverged considerably in Isoetes relative to flowering plants. This suggests the existence of more evolutionary paths to CAM than previously recognized.

plant biology↗

bioRxiv2019

Computational design of a modular protein sense/response system

Sensing and responding to signals is a fundamental ability of living systems, but despite remarkable progress in computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here we describe a generalizable computational strategy for designing sensor/actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation via split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site matches the design model with atomic accuracy. Our computational design strategy opens broad avenues to link biological outputs to new signals.\n\nOne Sentence SummaryAn engineering strategy to design modular synthetic signaling systems that respond to new small molecule inputs.

biophysics↗