Biology subjects

Pearson, C. A.

Publications and source records attributed to Pearson, C. A..

6 recordsLinked to original sources

bioRxiv2025

Cryopreservation of Human Cortical Organoids Using Vitrification.

Cryopreservation at ultra-low temperatures is a valuable tool for preserving cells and tissues used in research. However, few protocols exist for the preservation of brain organoid models. Current methods for preserving human cortical organoids (hCOs) rely on conventional slow cooling approaches with organoids suspended in a medium containing a cocktail of cryoprotectants. In contrast, we have optimized a vitrification technique previously used to cryopreserve human embryos and oocytes for application to hCOs. We have successfully cryopreserved hCOs that were generated by two different protocols. The vitrified organoids demonstrate a growth rate, cytoarchitecture, cell type composition and electrical activity comparable to non-vitrified controls. Our hCO cryopreservation method provides a useful alternative approach for bio-banking and cross-institutional collaboration using cortical organoids as their model system. Highlights- Human pluripotent stem cell (hPSC) derived hCOs can be cryopreserved using vitrification. - Vitrified hCOs develop similarly to non-vitrified controls. - Vitrified hCOs can be stored long-term and shipped to other institutions. MotivationMany methods of cryopreservation have been developed for the maintenance of cell lines, organoid models and tissues. Most organoid models have been successfully preserved using conventional slow-cooling methods; however, human cortical organoids have been difficult to preserve. Our findings demonstrate that the vitrification of cortical organoids preserves their structure, cell type diversity and function upon rewarming and continued culture.

neuroscience↗

bioRxiv2023

Improving modelling for epidemic responses: reflections from members of the UK infectious disease modelling community on their experiences during the COVID-19 pandemic

The COVID-19 pandemic both relied and placed significant burdens on the experts involved from research and public health sectors. The sustained high pressure of a pandemic on responders, such as healthcare workers, can lead to lasting psychological impacts including acute stress disorder, post-traumatic stress disorder, burnout, and moral injury, which can impact individual wellbeing and productivity. As members of the infectious disease modelling community, we convened a reflective workshop to understand the professional and personal impacts of response work on our community and to propose recommendations for future epidemic responses. The attendees represented a range of career stages, institutions, and disciplines. This piece was collectively produced by those present at the session based on our collective experiences. Key issues we identified at the workshop were lack of institutional support, insecure contracts, unequal credit and recognition, and mental health impacts. Our recommendations include rewarding impactful work, fostering academia-public health collaboration, decreasing dependence on key individuals by developing teams, increasing transparency in decision-making, and implementing sustainable work practices. Despite limitations in representation, this workshop provided valuable insights into the UK COVID-19 modelling experience and guidance for future public health crises. Recognising and addressing the issues highlighted is crucial, in our view, for ensuring the effectiveness of epidemic response work in the future.

scientific communication and education↗

bioRxiv2022

Foxp1 acts upstream of Vegfa, suppresses cortical angiogenesis, and promotes hypoxia in radial glia.

Radial glia progenitors within the cerebral cortex undergo a characteristic switch between symmetric self-renewing cell divisions early in development and asymmetric neurogenic divisions at later times, yet the mechanisms controlling this transition remain unclear. Previous work has shown that the autism-linked transcription factor Foxp1 is endogenously expressed by early but not late radial glia, and both loss and gain of Foxp1 can alter their neural progenitor activities and fate choices. Here, we show that premature loss of Foxp1 leads to an increase in transcriptional programs regulating angiogenesis, glycolysis, and cellular responses to hypoxia. These changes coincide with an elevation in Vegfa expression in radial glia and precocious vascular network development. Thus, the endogenous decline in Foxp1 expression appears to orchestrate changes in the tissue environment adjacent to radial glia that influence their metabolic state which in turn can alter their self-renewal and neurogenic capacities.

developmental biology↗

bioRxiv2019

Serostatus Testing & Dengue Vaccine Cost-Benefit Thresholds

The World Health Organisation currently recommends pre-screening for past infection prior to administration of the only licensed dengue vaccine, CYD-TDV. Using a bounding analysis, we show that despite additional testing costs, this approach can improve the economic viability of CYD-TDV: effective testing reduces unnecessary vaccination costs while increasing the health benefit for vaccine recipients. When testing is cheap enough, those trends outweigh additional screening costs and make test-then-vaccinate strategies net-beneficial in many settings.\n\nWe derived these results using a general approach for determining price thresholds for testing and vaccination, as well as indicating optimal start and end ages of routine test-then-vaccinate programs. This approach only requires age-specific seroprevalence and a cost estimate for second infections. We demonstrate this approach across settings commonly used to evaluate CYD-TDV economics, and highlight implications of our simple model for more detailed studies. We found trends showing test-then-vaccinate strategies are generally more beneficial starting at younger ages, and that in some settings multiple years of testing can be more beneficial than only testing once, despite increased investment in testing.

epidemiology↗

bioRxiv2018

Foxp1 controls neural stem cell competence and bias towards deep layer cortical fate.

SUMMARYThe laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. We identify critical roles for Foxp1 in maintaining RG identity and gating the temporal competency for early neurogenesis. High levels of Foxp1 are associated with early aRG and are required to promote proliferation and influence cell division symmetry, favoring aRG expansion and production of early born neurons. The potent pro-progenitor functions of Foxp1 are revealed through its ability to preserve a population of cells with aRG identity throughout development and extend the early neurogenic period into postnatal life. Foxp1 further promotes the formation of cells resembling basal RG (bRG), a progenitor group implicated in the increased size and complexity of the human cortex. Consistent with this role, we show that FOXP1 is associated with the initial formation and expansion of bRG during human corticogenesis.\n\nHIGHLIGHTSO_LIFoxp1 is transiently expressed by aRG during the early phase of corticogenesis\nC_LIO_LIFoxp1 promotes self-renewing vertical cell divisions and aRG maintenance\nC_LIO_LIFoxp1 gates the time window of deep layer neurogenesis\nC_LIO_LIEctopic Foxp1 expression can elicit bRG formation\nC_LI

developmental biology↗

bioRxiv2017

Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics

During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We address the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we define the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation, and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.

developmental biology↗