Biology subjects

Lukoseviciute, M.

Publications and source records attributed to Lukoseviciute, M..

5 recordsLinked to original sources

bioRxiv2026

Reconstitution of the Spinal Cord Injury Microenvironment in Adult Neural Stem Cell-Derived Organoids

Following spinal cord injury, endogenous neural stem cells (NSCs) derived from ependymal cells become activated but fail to functionally regenerate the tissue, largely because the injury microenvironment constrains their differentiation toward glial fates. Dissecting how specific niche components drive these outcomes has remained challenging in vivo, and current neural organoid models predominantly recapitulate embryonic neurodevelopment rather than the adult injury context. Here we describe neuroids - a modular organoid system built from injury-activated adult spinal cord ependymal NSCs that spontaneously differentiate into neurons, astrocytes, and to some degree oligodendrocytes within a self-organised 3D structure. Using a bottom-up approach, we reconstruct the injury niche by incorporating meningeal fibroblasts and primary adult microglia, individually and in combination. Fibroblasts accumulate in the organoid core, deposit extracellular matrix (ECM), and trigger reactive astrocyte responses mirroring in vivo scar organisation, while microglia integrate throughout, adopt heterogeneous activation states, and remain functionally active. Their combined incorporation further enhances ECM deposition and promotes oligodendrocyte lineage commitment, suggesting cooperative niche interactions. Single-nucleus multiome profiling and trajectory inference show that these injury-like conditions shift NSC differentiation away from neuronal programs toward proliferative and astroglial states, recapitulating NSC behaviour after injury in vivo. Ligand-receptor analysis implicates microglia-derived TGF{beta}, WNT, and ECM-associated signals as candidate drivers of this gliogenic bias. Together, neuroids provide a tractable platform to study how the adult injury niche regulates endogenous NSC fate, and to identify strategies that simultaneously redirect these cells toward regeneration while targeting the fibrotic scar - two barriers that together prevent functional recovery after spinal cord injury.

neuroscience↗

bioRxiv2021

Segregation of neural crest specific lineage trajectories from a heterogeneous neural plate border territory only emerges at neurulation

The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harbouring neural crest and cranial placode progenitors. Here we profile avian epiblast cells as a function of time using single-cell RNA-seq to define transcriptional changes in the emerging neural plate border. The results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridisation. Developmental trajectory analysis shows that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker Pax7 contribute to multiple lineages, and a subset of premigratory neural crest cells shares a transcriptional signature with their border precursors. Together, our results suggest that cells at the neural plate border remain heterogeneous until early neurulation, at which time progenitors become progressively allocated toward defined lineages.

developmental biology↗

bioRxiv2021

Neuromesodermal progenitor origin of trunk neural crest in vivo

Neural crest (NC) is a vertebrate-specific population of multipotent embryonic cells predisposed to diverse derivatives along the anteroposterior (A-P) axis. Only cranial NC progenitors give rise to ectomesenchymal cell types, whereas trunk NC is biased for neuronal cell fates. By integrating multimodal single-cell analysis, we provide evidence for divergent embryonic origins of cranial vs. trunk NC that explain this dichotomy. We show that the NC regulator foxd3 is heterogeneously expressed across the A-P axis and identify its specific cranial and trunk autoregulatory enhancers. Whereas cranial-specific enhancer is active in the bona fide NC, the trunk foxd3 autoregulatory element surprisingly marked bipotent tailbud neuromesodermal progenitors (NMps). We integrated NMp single cell epigemomics and trasncriptomics data and for the first time reconstructed anamniote NMp gene regulatory network. Moreover, using pseudotime and developmental trajectory analyses of NMps and NC during normal development and in foxd3 mutants, we demonstrate an active role for foxd3 in balancing non-cranial NC and NMp fates during early embryonic development. Strikingly, we show that a portion of posterior NC in the developing zebrafish embryo is derived from the pro-neural NMps. This suggests a common embryonic origin of trunk NC and NM progenitors that is distinct from cranial NC anlage, and elucidates pro-neural bias of trunk NC.

developmental biology↗

bioRxiv2019

Nanoscale dynamics of cholesterol in the cell membrane

Cholesterol constitutes approximately 30-40% of the mammalian plasma membrane -- a larger fraction than any other single component. It is a major player in numerous signalling processes as well as molecular membrane architecture. However, our knowledge on dynamics of cholesterol in the plasma membrane is limited which restricts our understanding of the mechanisms regulating its involvement in cell signalling. Here, advanced fluorescence imaging and spectroscopy approaches were applied on in vitro (model membranes) and in vivo (live cells and embryos) membranes to systematically study the nanoscale dynamics of cholesterol in biological membranes. The results show that cholesterol diffuses faster than phospholipids in live membranes, but not in model membranes. The data indicate that diffusion of cholesterol and phospholipids is not correlated with membrane domain partitioning. Instead, our data show that the fast diffusion of cholesterol is due to its nanoscale interactions and localization in the membrane.

biophysics↗

bioRxiv2017

From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo

The neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3-mutant versus wild type cells in vivo to define the gene regulatory circuits controlling NC specification. Together with global binding analysis obtained by foxd3 biotin-ChIP and single cell profiles of foxd3-expressing premigratory NC, our analysis shows that during early steps of NC formation, foxd3 acts globally as a pioneer factor to prime the onset of genes regulating NC specification and migration by re-arranging the chromatin landscape, opening cis-regulatory elements and reshuffing nucleosomes. Strikingly, foxd3 then switches from an activator to its canonical role as a transcriptional repressor. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from permissive to repressive nucleosome/chromatin organisation to maintain stemness and define cell fates.

developmental biology↗