The heart is a complex organ composed of multiple cell and tissue types. Cardiac cells from different regions of the growing embryonic heart exhibit distinct patterns of gene expression, which are thought to contribute to heart development and morphogenesis. Single cell RNA sequencing allows genome-wide analysis of gene expression at the single cell level. Here, we have analyzed cardiac cells derived from early stage developing hearts by single cell RNA-seq and identified cell cycle gene expression as a major determinant of transcriptional variation. Within cell cycle stage-matched CMs from a given heart chamber, we found that CMs in the G2/M phase downregulated sarcomeric and cytoskeletal markers. We also identified cell location-specific signaling molecules that may influence the proliferation of other nearby cell types. Our data highlight how variations in cell cycle activity selectively promote cardiac chamber growth during development, reveal profound chamber-specific cell cycle-linked transcriptional shifts, and open the way to deeper understanding of pathogenesis of congenital heart disease.

By using comparative genomic hybridization (CGH), we characterized the genetic pro®les of 36 VHL-related pheochromocytomas. We then compared the results with those of sporadic and MEN 2-related pheochromocytomas. In 36 VHL-related tumors, loss of chromosome 3 and chromosome 11 were found in 34 tumors (94%) and 31 tumors (86%), respectively. There was signi®cant concordance of deletions in chromosomes 3 and 11 (Kappa=0.64, P=0.0095), suggesting that they are involved in two di erent but necessary and complementary genetic pathways. The loss of chromosome 11 appeared to be speci®c for VHL-related pheochromocytoma as it was not present in any of the 10 VHL-related CNS hemangioblastomas studied and was signi®cantly less common when compared with (a) sporadic pheochromocytomas from previously published results (13%; P=50.0001), and (b) MEN 2-related pheochromocytomas from this and previously published studies (30%; P=0.0012). In summary, this is the ®rst report of a novel consistent genetic alteration that is selected and speci®c for VHL-related pheochromocytoma, besides the two hits of the VHL gene.

The incidence of most pancreatic neoplasms has changed a little; however, nonfunctional neuroendocrine neoplasms increased greater than 2-fold. The etiology of this change is unclear.