Biology subjects

Tang, S. S.

Publications and source records attributed to Tang, S. S..

5 recordsLinked to original sources

bioRxiv2026

Human Choroid Plexus Organoids Progress to Postnatal-like Maturation and Reveal a Closing Window of Developmental Plasticity

The choroid plexus (ChP) produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier, yet the developmental programme driving its maturation in humans remains poorly understood. Using a 15-timepoint single-cell RNA sequencing atlas of human ChP organoids benchmarked against human tissue, we resolve an ordered differentiation process comprising cell cycle exit, ciliogenesis and ion transporter expression. Maturation culminates in a transcriptional state with features of human adult ChP, establishing the first in vitro ChP model to reach postnatal-like milestones. Centrosome proteomics identified previously uncharacterised, stage-specific regulators of ciliogenesis. To probe developmental plasticity, we perturbed ChP organoids with valproic acid (VPA), a clinically used antiepileptic and established teratogen. Early VPA-mediated disruption of multiciliogenesis and secretion recovered upon drug withdrawal, whereas late treatment washout resulted in persistent impairment of mature transporters. Together, these findings resolve the developmental programme by which the ChP reaches functionally mature identity and identify a stage-dependent plasticity window during its maturation.

developmental biology↗

bioRxiv2026

Fluid shear magnitude, mechanical history and actin-sensitive coupling shape Piezo1 signalling

Mechanical forces shape cell behaviour, yet how Piezo1-associated responses encode force magnitude, recent mechanical history and cytoskeletal context under repeated fluid shear remains unclear. We combined defined fluid shear stress (FSS) with GenEPi, a genetically encoded reporter of Piezo1-proximal Ca2+ entry, in engineered XLGenEPi-HEK293T monolayers to resolve mechanically evoked responses at single-cell and population scales. GenEPi responses increased with FSS magnitude but showed diminishing response gain at higher shear. Repeated submaximal FSS produced history-dependent attenuation and reduced temporal coordination, with higher FSS accelerating the early phase of attenuation. Low-dose Latrunculin A, without significantly reducing bulk F-actin abundance, converted sustained FSS-evoked signalling into a brief, decay-dominated response while largely preserving peak responses to Yoda1. These findings show that Piezo1-associated signalling is shaped over minutes by force magnitude, recent mechanical history and actin-sensitive mechanical coupling, providing a quantitative framework for understanding mechanotransduction under sustained and repeated mechanical stimulation.

biophysics↗

bioRxiv2026

A TSST 1 structural motif disrupts endothelial programs required for vascular regeneration.

Staphylococcus aureus causes profound vascular damage during infection, where it inflicts vascular injury across organs and generates lesions that fail to heal. Superantigens are major virulence factors in S. aureus infections, yet their direct effects on vascular repair remain unclear. We provide evidence that TSST-1 disrupts endothelial regeneration through coordinated mechanisms. TSST-1 interferes with collective directed migration, impairing endothelial cell directional persistence and preventing re-endothelialization in vitro. These defects stem from cytoskeletal disorganization, characterized by stress fiber accumulation and loss of lamellipodia, and broad suppression of motility-associated secreted factors. In an ex vivo aortic ring assay, TSST-1 suppresses angiogenic sprouting and generates dysmorphic vascular networks. Proteomic profiling reveals a shift toward matrix rigidity, adhesion stabilization, and overall suppression of angiogenesis. These activities map to a conserved dodecapeptide motif. Hence, TSST-1 suppression of vascular repair may convert sites of tissue injury into persistently non-healing niches suited for S. aureus persistence.

cell biology↗

bioRxiv2021

Staphylococcus aureus β-toxin exerts anti-angiogenic effects by inhibiting re-endothelialization and neovessel formation

Staphylococcus aureus is the causative agent of numerous severe human infections associated with significant morbidity and mortality worldwide. S. aureus often targets the vascular endothelium to interfere with proper host responses during invasive infections. In this study, we provide evidence that S. aureus {beta}-toxin inhibits wound repair mechanisms in human endothelial cells by preventing cell proliferation and migration. These findings were confirmed in a rabbit aortic explant model where {beta}-toxin impedes sprout formation. Decreased cell proliferation was accompanied by decreased production of the angiogenic proteins endothelin-1, IGFBP-3, thrombospondin-1, TIMP-1, and TIMP-4. Meanwhile, inhibited wound repair was marked by increased HGF secretion from endothelial cells, likely a marker of endothelial cell damage. Together, these findings establish a mechanistic role for {beta}-toxin where it inhibits proper tissue repair processes that likely promote S. aureus infective niche.

microbiology↗

bioRxiv2021

Diverse human astrocyte and microglial transcriptional responses to Alzheimer's pathology

To better define roles that astrocytes and microglia play in Alzheimers disease (AD), we used single-nuclei RNA sequencing to comprehensively characterize transcriptomes in astrocyte and microglia nuclei isolated post mortem from neuropathologically-defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid and pTau expression. Astrocytes were enriched for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, proteostasis and autophagy were highly enriched in microglia and perivascular macrophages. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.

neuroscience↗