Search

Neural progenitors show a strong tendency to undergo apoptosis in response to DNA damage, and both impaired DNA repair and increased neural progenitor apoptosis are associated with microcephaly. Here we present an immunohistochemistry-based method for assessing DNA damage and apoptosis in the neonatal mouse brain. These methods are suitable for determining in specific experimental conditions the fractions of cells with DNA double-strand breaks, the fractions of cells undergoing apoptosis, or both. While DNA damage in neural progenitors can trigger apoptosis, inappropriate apoptosis may also result from other processes. Simultaneous analysis of DNA damage and apoptosis in mouse models of microcephaly can determine how genetic instability and cell death contribute to the observed phenotype., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Analysis of single-cell RNA sequencing typically includes the clustering of cells and subsequent determination of the population size of each cluster, relative to the whole. In an experimental setting, two or more conditions are compared to assess changes in cellular composition of the sampled tissue. Cluster populations are frequently normalized to the total number of cells from each replicate in order to facilitate comparisons. After normalization, they become interdependent fractions and therefore cannot be compared using individual t-tests. Here we describe the use of Dirichlet regression to compare changes in cellular composition between two or more conditions when multiple biological replicates (three or more) are sampled under each condition. We provide an example of R code to conduct a similar analysis and interpret the results., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

New targets for brain tumor therapies may be identified by mutations that cause hereditary microcephaly. Brain growth depends on the repeated proliferation of stem and progenitor cells. Microcephaly syndromes result from mutations that specifically impair the ability of brain progenitor or stem cells to proliferate, by inducing either premature differentiation or apoptosis. Brain tumors that derive from brain progenitor or stem cells may share many of the specific requirements of their cells of origin. These tumors may therefore be susceptible to disruptions of the protein products of genes that are mutated in microcephaly. The potential for the products of microcephaly genes to be therapeutic targets in brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6, and ATR. Treatments that disrupt these proteins may open new avenues for brain tumor therapy that have increased efficacy and decreased toxicity., (© 2018 WILEY Periodicals, Inc.)