RESUMO
Broad heterogeneity in pancreatic ß-cell function and morphology has been widely reported. However, determining which components of this cellular heterogeneity serve a diabetes-relevant function remains challenging. Here, we integrate single-cell transcriptome, single-nuclei chromatin accessibility, and cell-type specific 3D genome profiles from human islets and identify Type II Diabetes (T2D)-associated ß-cell heterogeneity at both transcriptomic and epigenomic levels. We develop a computational method to explicitly dissect the intra-donor and inter-donor heterogeneity between single ß-cells, which reflect distinct mechanisms of T2D pathogenesis. Integrative transcriptomic and epigenomic analysis identifies HNF1A as a principal driver of intra-donor heterogeneity between ß-cells from the same donors; HNF1A expression is also reduced in ß-cells from T2D donors. Interestingly, HNF1A activity in single ß-cells is significantly associated with lower Na+ currents and we nominate a HNF1A target, FXYD2, as the primary mitigator. Our study demonstrates the value of investigating disease-associated single-cell heterogeneity and provides new insights into the pathogenesis of T2D.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Multiômica , Cromatina , Epigenômica , Perfilação da Expressão Gênica , Fator 1-alfa Nuclear de HepatócitoRESUMO
Aphantasia, the loss of mental imagery, is a rare disorder and even more infrequent when acquired. No previous cases have been identified that were caused by transplant-related treatment. We describe a case of acquired aphantasia in a 62-year-old male with refractory IgG kappa multiple myeloma after receiving an autologous stem cell transplant (ASCT) following high-dose melphalan with a complicated hospital admission. The etiology of aphantasia remains unidentified, but we provide viable explanations to include direct effects from ASCT treatment and indirect effects from transplant-related complications.
RESUMO
Reticulate evolution is thought to accelerate the process of evolution beyond simple genetic drift and selection, helping to rapidly generate novel hybrids with combinations of adaptive traits. However, the long-standing dogma that reticulate evolutionary processes are likewise advantageous for switching ecological niches, as in microbial pathogen host switch events, has not been explicitly tested. We use data from the influenza genome sequencing project and a phylogenetic heuristic approach to show that reassortment, a reticulate evolutionary mechanism, predominates over mutational drift in transmission between different host species. Moreover, as host evolutionary distance increases, reassortment is increasingly favored. We conclude that the greater the quantitative difference between ecological niches, the greater the importance of reticulate evolutionary processes in overcoming niche barriers.