COVID-19 has illuminated how racial inequities across multiple institutions in the United States have converged and resulted in profound and lasting negative impacts on people and communities of color. Disparities in the treatment of Native (Indigenous) Americans, African (Black) Americans, and Latinx individuals in the United States concomitant with health disparities more prevalent in these populations have resulted in COVID-19 death rates that have been consistently higher than that of white counterparts and at rates that are significantly higher than their percentage of the population. While reports have focused have necessarily focused on the despair in these communities and the disparities in case and death rates, we report on the historical resilience of these communities and how this has been used to mobilize interventions in these communities that have served to mitigate the negative impact of COVID-19.

Hydrocephalus is a prevalent condition among newborns leading to substantial neurocognitive and motor impairment. Novel therapies are needed to supplant invasive surgeries but identifying targetable cells and pathways remains a hurdle to devising alternative pharmacological options. Multiciliated ependymal cells (MECs) promote cerebrospinal fluid flow within brain ventricles and their dysfunction is associated with various forms of hydrocephalus. Here we show that an acute exposure to TNF-α strongly impairs the conversion of ependymal cell radial glial progenitors (ecRGPs) into MECs. Inhibition of MEC differentiation was correlated with elevated expression levels of notch pathway effectors normally downregulated prior to the transition of ecRGPs into MECs. TNF-α inhibited Multicilin gene upregulation along with downstream genes critical for centriole amplification and multicilia formation resulting in cells with greatly diminished basal bodies and multicilia. Treatment with notch inhibitor, DBZ, either in parallel with TNF-α or sequentially days later rescued MEC differentiation and expression of genes required for multicilia formation. These results provide a rationale for how TNF-α can impair MEC development, and they offer a targetable pathway to the treatment of some forms of hydrocephalus.