Biomedical subjects

Sofie R Salama

Publications and source records attributed to Sofie R Salama.

2 recordsLinked to original sources

PubMed2025

Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.

The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release. We identify human-specific gene expression changes related to axonal transport of mitochondria and reactive oxygen species buffering and candidate cis- and trans-regulatory mechanisms underlying gene expression divergence. Our findings are consistent with a model of evolved neuroprotection in response to tradeoffs related to brain expansion and could contribute to the discovery of therapeutic targets and strategies for treating disorders involving the dopaminergic system.

Brain evolution↗

PubMed2025

Consistently processed RNA sequencing data from 50 sources enriched for pediatric data.

Larger cohorts improve the power of tumor gene expression analysis, but the signal is muddied if datasets are processed using different methods or have inaccurate metadata. Here we present five compendia containing consistently processed gene expression data derived from 16,446 diverse RNA sequencing datasets. To create the compendia, we obtained access to RNA sequence data from repositories containing public data as well as clinical partners with access to non-published data. We then assessed the quality, quantified gene expression, harmonized clinical metadata, and released the expression values and metadata without access restrictions. These datasets have been used for diverse projects ranging from identifying similarities between tumor types to assessing how well cell lines recapitulate tumors. They have also been used for n-of-1 analysis to identify genes with unusual expression patterns in a single sample and to infer molecular diagnosis. The comparison to new data is enabled by our dockerized, freely available pipeline. The compendia have been cited in at least 20 publications.

Humans↗