Biology subjects

Vinsland, E.

Publications and source records attributed to Vinsland, E..

5 recordsLinked to original sources

bioRxiv2025

Organotypic Timelapse recording with Transcriptomic Readout (OTTR) links cell behaviour to cell identity in human tissues

Linking dynamic cellular behaviour to molecular states in intact human tissue remains challenging because during live imaging only limited molecular information can be captured while high-dimensional molecular measurements are destructive. Here we describe Organotypic Timelapse recording with Transcriptomic Readout (OTTR), which integrates week-long live imaging of sparsely labelled organotypic slice cultures with highly multiplexed in situ spatial transcriptomics. We applied OTTR to primary human glioblastoma and fetal cortical tissues. Using sparse labelling, we tracked the migration, proliferation, and lineage of tens of thousands of individual cells per sample. Following live imaging, precision resectioning and alignment allowed us to perform spatial transcriptomics on the very same tissue, thereby preserving the link between dynamic cell behaviours and transcriptomic states. We used OTTR to quantify cell-type specific migration patterns, lineage trees and the behaviour of cells near vasculature. OTTR provides a powerful, broadly applicable method for investigating the complex interplay between cell behaviour and molecular state in human tissues.

molecular biology↗

bioRxiv2025

Cell atlas of the developing human meninges reveals a dura origin of meningioma

The vertebrate central nervous system is enveloped by the meninges, consisting of the pia, arachnoid, and dura layers. The arachnoid is hypothesised to give rise to the most common primary intracranial tumours, meningiomas. However, molecular evidence supporting this hypothesis is lacking. There are no effective medical therapies to treat meningiomas that are resistant to local interventions, encumbered by our limited understanding of their cellular origin. To address this limitation in our understanding of meningioma biology, we generated a comprehensive reference single cell and spatial transcriptomic atlas of human fetal meninges at post-conceptional weeks 5-13. We found that the meningeal layers develop concurrently, and identified an inner CDH1-positive dura cell layer expressing tight junction genes consistent with barrier function. We show that transcriptionally, meningioma cells resemble dura-lineage cells, and that common meningioma driver genes were expressed preferentially in the dura lineage. Our findings suggest that meningiomas originate from dura lineage cells. HIGHLIGHTSO_LIscRNA-seq and spatial transcriptomics reveals architecture of human fetal meninges development C_LIO_LIMeningeal layers are formed concurrently, by a gradual refinement of cell states C_LIO_LIA CDH1+ inner dura sublayer expresses tight junction genes like the arachnoid barrier C_LIO_LIMeningioma tumours likely originate from inner dura lineage cells, not arachnoid C_LI

developmental biology↗

bioRxiv2022

Comprehensive cell atlas of the first-trimester developing human brain

The adult human brain likely comprises more than a thousand kinds of neurons, and an unknown number of glial cell types, but how cellular diversity arises during early brain development is not known. Here, in order to reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics to uncover cell states and trajectories in human brains at 5 - 14 post-conceptional weeks (p.c.w.). We identified twelve major classes and over 600 distinct cell states, which mapped to precise spatial anatomical domains at 5 p.c.w. We uncovered detailed differentiation trajectories of the human forebrain, and a surprisingly large number of region-specific glioblasts maturing into distinct pre-astrocytes and pre-oligodendrocyte precursor cells (pre-OPCs). Our findings reveal the emergence of cell types during the critical first trimester of human brain development.

developmental biology↗

bioRxiv2022

Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis

Mechanistic target of rapamycin (mTOR) is a protein kinase that integrates multiple inputs to regulate anabolic cellular processes. mTOR complex I (mTORC1) has key functions in growth control, autophagy and metabolism. Much less is known about the signalling components that act downstream of mTORC1 that regulate cellular morphology, a vital determinant of cellular function. Here we show that the RNA-binding protein Unkempt, a key regulator of cellular morphogenesis, is a novel substrate mTORC1. We find that Unkempt phosphorylation is regulated by nutrient levels and growth factors via mTORC1. Furthermore, Unkempt physically interacts with and is directly phosphorylated by mTORC1 through binding to the regulatory-associated protein of mTOR, Raptor. Phosphorylation of Unkempt, which we find is mTORC1-dependent in cultured mammalian cell lines as well as in primary tissues, occurs largely within the highly serine-rich intrinsically disordered region of Unkempt. Importantly, mutation analysis of this region indicates that phosphorylation inhibits the ability of Unkempt to induce a bipolar morphology. Our findings reveal a novel molecular link between mTORC1 signalling and cellular morphogenesis.

neuroscience↗

bioRxiv2020

Molecular architecture of the developing mouse brain

The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell-cell interactions, and intrinsic genetic programs that result in the generation of likely more than a thousand distinct cell types. Therefore, a complete understanding of mammalian brain development requires systematic mapping of cell states covering the entire relevant spatiotemporal range. Here we report a comprehensive single-cell transcriptome atlas of mouse brain development spanning from gastrulation to birth. We identified almost a thousand distinct cellular states, including the initial emergence of the neuroepithelium, a rich set of region-specific secondary organizers and a complete developmental program for the functional elements of the brain and its enclosing membranes. We used the atlas to directly test the hypothesis that human glioblastoma reflects a return to a developmental cell state. In agreement, most aneuploid tumor cells matched embryonic rather than adult types, while karyotypically normal cells predominantly matched adult immune cell types.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗