Biology subjects

Maynard, T. M.

Publications and source records attributed to Maynard, T. M..

3 recordsLinked to original sources

bioRxiv2026

SPACKLE: A spatial-first framework for multi-layer spatial transcriptomic analysis

Background The emergence of accessible spatial transcriptomic platforms such as 10x Genomics Visium HD and Xenium has created demand for analysis tools that can handle the complexity and scale of spatial datasets. Current frameworks approach spatial data primarily as an extension of single-cell RNA-seq pipelines, where spatial coordinates are retained as metadata rather than treated as a first-class organizing principle. As a result, common tasks such as multi-modal data alignment, region-of-interest selection, and cross-resolution visualization require manually managing disparate data types, coordinates, and scales, making spatial analysis unnecessarily time-consuming and error-prone. Results We present platpy (pipeline for layered analysis of transcriptomics), a Python-based "spatial-first" framework that treats absolute physical micron coordinates as the organizing principle for all data types. All data -- morphology images, transcript point clouds, expression matrices, segmented cells, and user-defined regions -- are stored as typed objects ("Channels") that carry their own spatial metadata, keeping all layers in automatic registration regardless of platform, resolution, or analysis operation. Two complementary interfaces simplify access to underlying data: the ViewPort, a compositing engine for efficient multi-channel visualization, and the DataPort, which extracts raw data in its native format for downstream analysis. A set of spatial analysis tools demonstrates the practical benefits of the framework, including ROI-based expression binning, cortical unfolding, and sub-micron fine alignment of transcript and image data. The use of modern Python data management methods helps maintain the efficiency of the framework, allowing for quick visualizations and analysis with a low memory footprint. Conclusions Platpy is designed to complement rather than replace widely used tools in the spatial analysis ecosystem (scanpy, squidpy, CellPose, StarDist), by handling the spatial mechanics of large datasets so that the analyst can focus on the biology. Platpy is freely available under the MIT license at https://github.com/maynardt/platpy.

bioinformatics↗

bioRxiv2025

22q11 deletion selectively alters progenitor states and projection neuron identities in the developing cerebral cortex

The developmental origin of Layer 2/3 projection neuron (PN) pathology in the frontal association cortex due to heterozygous 22q11 gene deletion--the genetic foundation of elevated risk for schizophrenia and related psychiatric disorders in 22q11.2 Deletion Syndrome (22q11DS)--reflects cell state-dependent, temporally restricted vulnerability of transcriptionally diverse subsets of intermediate progenitors and neuroblasts. The molecular and cell biological consequences of these evanescent state-dependent changes include divergent proliferative capacity of the most highly proliferative progenitors, enhanced neurogenic gene expression, altered DNA methylation, and increased numbers of immediate neuroblast progeny at peak neurogenesis in fetal frontal cortex of the LgDel 22q11DS mouse model. These altered cell states prefigure a post-natal cohort of upper layer PNs generated at the peak of Layer 2/3 PN genesis--not before or after--whose frequencies are significantly diminished and molecular identities are substantially divergent in medial frontal association, but not primary somatosensory or visual cortices. Thus, frontal association cortices in 22q11DS and schizophrenia more broadly may be pathogenic targets due to vulnerabilities of expanded, highly proliferative, transcriptionally dynamic populations of intermediate progenitors that increase L2/3 PN frequency to enhance cortico-cortical connectivity.

neuroscience↗

bioRxiv2021

Lineage, Identity, and Fate of Distinct Progenitor Populations in the Embryonic Olfactory Epithelium

We defined a temporal dimension of precursor diversity and lineage in the developing mouse olfactory epithelium (OE) at mid-gestation that results in genesis of distinct cell classes. Slow, symmetrically dividing Meis1+/ Pax7+ progenitors in the early differentiating lateral OE give rise to small numbers of Ascl1+ precursors in the dorsolateral and ventromedial OE. Few of the initial progeny of the Ascl1+ precursors immediately generate olfactory receptor neurons (ORNs). Instead, most early progeny of this temporally defined precursor cohort, labeled via temporally discreet tamoxifen-dependent Ascl1Cre-driven recombination, populate a dorsomedial OE domain comprised of proliferative Ascl1+ as well as Ascl1-cells from which newly generated ORNs are mostly excluded. The most prominent early progeny of these Ascl1+ OE precursors are migratory mass cells associated with the nascent olfactory nerve (ON) in the frontonasal mesenchyme. These temporal, regional and lineage distinctions are matched by differences in proliferative capacity and modes of division in isolated, molecularly distinct lateral versus medial OE precursors. By late gestation, the progeny of the temporally and spatially defined Ascl1+ precursor cohort include few proliferating precursors. Instead, these cells generate a substantial subset of OE sustentacular cells, spatially restricted ORNs, and ensheathing cells associated with actively growing as well as mature ON axons. Accordingly, from the earliest stages of OE differentiation, distinct temporal and spatial precursor identities provide a template for acquisition of subsequent OE and ON cellular diversity.

developmental biology↗