Biology subjects

Hou, A.

Publications and source records attributed to Hou, A..

4 recordsLinked to original sources

bioRxiv2026

A Single-Cell and Spatial 3D Multi-omic Atlas of Developing Human Basal Ganglia and Inhibitory Neurons

The human basal ganglia (BG), subcortical nuclei fundamental to motor regulation and cognitive modulation, is constructed from neurons produced during gestation in the adjacent ganglionic eminences (GEs). GEs are transient structures in the ventral prenatal brain that also generate GABAergic inhibitory neurons which migrate to destinations in the BG, cortex and other destinations. This study aims to elucidate the epigenomic and 3D-genomic dynamics involved in the specification and maturation of GEs and GE-derived neurons, using single-nucleus methyl-3C sequencing (snm3C-seq), highly-multiplexed spatial transcriptomics, and chromatin+RNA single-molecule imaging. Our multi-modal data support a heterogeneous temporal progression across GE subregions, with the lateral GE (LGE) showing declining neurogenic activity in mid-gestation and caudal GE (CGE) exhibiting ongoing developmental progression through infancy. We identified regulatory programs that specify subtypes of BG principal cells, medium spiny neurons (MSN), via synchronized maturation of the 3D-epigenome. In infant brains, we found a transient short-range enriched (SE) chromatin conformation during the transition between oligodendrocyte progenitors (OPCs) and oligodendrocytes (ODCs), and a temporary shift toward Long-range Enriched (LE) chromatin conformation in projection neurons, extending previous works showing the differentiation of neurons and glial cells is associated with permanent SE and LE conformation, respectively. Lastly, we found that gene regulatory regions active in MSNs were enriched in loci associated with genetic risk for neuropsychiatric disease. Our study delineates the highly complex, lineage-specific 3D genomic dynamics in ventral progenitors and basal ganglia populations of the perinatal human brain. HighlightsO_LIJoint 3D genome and DNA methylome analysis of ventral brain progenitor zones C_LIO_LIHeterogeneous developmental progressions of the ganglionic eminences C_LIO_LIDistinct development dynamics and regulatory landscape of MSNs and interneurons C_LIO_LITransient remodeling of the 3D-genome in neurons and oligodendrocyte progenitors C_LI

genomics↗

bioRxiv2025

MERFISH+, a large-scale, multi-omics spatial technology resolves the molecular holograms of the 3D human developing heart

Hybridization-based spatial transcriptomics technologies have advanced our ability to map cellular and subcellular organization in complex tissues. However, existing methods remain constrained in gene coverage, multimodal compatibility, and scalability. Here, we present MERFISH+, an enhanced version of Multiplexed Error-Robust Fluorescence in Situ Hybridization (MERFISH), which integrates chemical probe anchoring in protective hydrogels with high-throughput microfluidics and microscopy. This optimized design supports robust and repeated hybridization cycles across an entire centimeter-scale tissue sample. MERFISH+ allowed to simultaneously quantify over 1,800 genes and resolve the 3D organization of chromatin loci and their associated epigenomic marks in developing human hearts. Using a generative integration framework for spatial multimodal data (Spateo-VI), we harmonized these MERFISH+ transcriptomic and chromatin data to reconstruct a 3D spatially-resolved multi-omic atlas of the developing human heart at subcellular resolution capturing 3.1 million cells across 34 distinct populations. This 3D atlas provides a holistic view of an entire organ enabling the characterization of 3D cellular neighborhoods and transcriptional gradients of substructures such as the descending arteries. Thus, MERFISH+ offers a robust, large-format platform for spatial multi-omics that enables high resolution mapping of gene expression at subcellular resolution and the characterization of cellular organization within 3D organs. One Sentence SummaryMERFISH+ is an spatial multi-omics platform that integrates hydrogel-based probe anchoring, automated high-throughput microfluidics, and large-format multimodal data production to enable comprehensive, subcellular resolution mapping of gene expression and chromatin organization across millions of cells within complex developing human organs. HighlightsO_LIMERFISH+ expands MERFISH capabilities to measure >1,800 genes and at whole-organ 3D imaging scale C_LIO_LICombines chemical probe anchoring with high-throughput volumetric microscopy and microfluidics C_LIO_LIGenerates a 3D molecular atlas of a developing human heart with > 3.1 million cells at subcellular resolution C_LIO_LIIntroduces Spateo-VI, a novel generative framework integrating 3D multimodal datasets C_LI

genomics↗

bioRxiv2021

SARS-CoV-2 wildlife surveillance in Ontario and Quebec, Canada

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is capable of infecting a variety of wildlife species. Wildlife living in close contact with humans are at an increased risk of SARS-CoV-2 exposure and if infected have the potential to become a reservoir for the pathogen, making control and management more difficult. ObjectiveTo conduct SARS-CoV-2 surveillance in urban wildlife from Ontario and Quebec, Canada, increasing our knowledge of the epidemiology of the virus and our chances of detecting spillover from humans into wildlife. MethodsUsing a One Health approach, we leveraged activities of existing research, surveillance, and rehabilitation programs among multiple agencies to collect samples from 776 animals from 17 different wildlife species between June 2020 and May 2021. Samples from all animals were tested for the presence of SARS-CoV-2 viral RNA, and a subset of samples from 219 animals across 3 species (raccoons, Procyon lotor; striped skunks, Mephitis mephitis; and mink, Neovison vison) were also tested for the presence of neutralizing antibodies. ResultsNo evidence of SARS-CoV-2 viral RNA or neutralizing antibodies was detected in any of the tested samples. ConclusionAlthough we were unable to identify positive SARS-CoV-2 cases in wildlife, continued research and surveillance activities are critical to better understand the rapidly changing landscape of susceptible animal species. Collaboration between academic, public and animal health sectors should include experts from relevant fields to build coordinated surveillance and response capacity.

pathology↗

bioRxiv2017

Releasing potential power of terpene synthases by a robust precursor supply platform

Approximately 76,000 discovered makes terpenoids the largest family of natural products in nature with widespread applications. The wide-spectrum of structural diversity of the terpenoids were largely due to the variable skeletons generated by terpene synthases. The number of terpene skeletons found in nature, however, were so much more than those conceivably generated from known terpene synthases and the limited characterized terpene synthases also make no chance for some useful terpenoids overproduction in microbe. Here, we first demonstrated that the promiscuous synthases in vivo can produce more variable terpenoid products by converting precursors of different lengths (C10, C15, C20, C25). This discovery was prompted by the development of an efficient in vivo platform by combining the two promiscuous terpene synthases and three prenyltransferases to generate 50 terpenoids, at least 3 ring systems of which were completely new. Furthermore, protein engineering was further integrated to enhance product diversity. Clearly, the work is expected to dramatically reshape the terpenoid research by widening the flexibility of the terpene synthases for the fresh discovery or creation of the new terpenoid compounds by skeleton reframing.

biochemistry↗