Biology subjects

Neel, M.

Publications and source records attributed to Neel, M..

3 recordsLinked to original sources

bioRxiv2024

Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model

Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) displayed canonical properties and dynamic multiciliated phenotypes that interacted with A{beta} uptake. Single dCPEC transcriptomes over time correlated well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlighted the direct CPEC origin from neuroepithelial cells. In addition, time series analyses defined metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contracted. These temporal patterns were then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest new dynamic models of ChP support for the developing human brain.

neuroscience↗

bioRxiv2021

Human Neural Stem Cells Differentiate and Integrate, Innervating Implanted zQ175 Huntington's Disease Mouse Striatum

Huntingtons disease (HD), a genetic neurodegenerative disorder, primarily impacts the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that hNSCs transplanted into the striatum of HD mouse models differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here we show that 8-month implantation of hNSCs into the striatum of zQ175 HD mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) and reduces mutant Huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry and electron microscopy demonstrates that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells. Remarkably, hNSCs receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.

neuroscience↗

bioRxiv2020

Recovery plans need better science to support decisions that allow species to decline in abundance but be recovered

The U.S. Endangered Species Act (ESA) is widely considered the strongest biodiversity conservation law in the world. Part of its strength comes from the mandate to use the best available science to make decisions under the law, including whether to list a species, setting the criteria for when a species can be considered recovered, and determining when those criteria have been met and a species can be delisted. Both biological status and threat factors are considered at each stage of the listing and delisting process. In most cases, conservation science would suggest that species at risk enough to be listed under the Act should be more abundant and secure at delisting than they were at listing. Surprisingly, we identified 130 ESA-listed species that the U.S. Fish and Wildlife Service could consider recovered with fewer populations or individuals than existed at the time of listing. We ask whether their ESA recovery plans present scientific data, rationale, or evidence to support a decline in abundance as part of recovery. We find that almost no plan clearly explains why a decline is allowed. Fewer than half of the plans provide scientific support for a decline in the form of literature references or modeling results. We recommend that the U.S. Fish and Wildlife Service and the National Marine Fisheries Service create a decision support system to inform when species can decline in abundance and still recover, including guidance on (a) the need to explicitly address the declines and (b) the science used to support the decisions.

ecology↗