Single-Cell Sequencing in Precision Medicine.

The application of next-generation sequencing in cancer genomics allowed for a better understanding of the genetics and pathogenesis of cancer. Single-cell genomics is a relatively new field that has enhanced our current knowledge of the genetic diversity of cells involved in the complex biological systems of cancer. Single-cell genomics is a rapidly developing field, and current technologies can assay a single cell's gene expression, DNA variation, epigenetic state, and nuclear structure. Statistical and computational methods are central to single-cell genomics and allows for extraction of meaningful information. The translational application of single-cell sequencing in precision cancer therapy has the potential to improve cancer diagnostics, prognostics, targeted therapy, early detection, and noninvasive monitoring. Furthermore, single-cell genomics will transform cancer research as even initial experiments have revolutionized our current understanding of gene regulation and disease.

Intrauterine growth restriction perturbs nucleosome depletion at a growth hormone-responsive element in the mouse IGF-1 gene.

Intrauterine growth restriction (IUGR) is a common human pregnancy complication. IUGR offspring carry significant postnatal risk for early-onset metabolic syndrome, which is associated with persistent reduction in IGF-1 protein expression. We have previously shown that preadolescent IUGR male mice have decreased hepatic IGF-1 mRNA and circulating IGF-1 protein at postnatal day 21, the age when growth hormone (GH) normally upregulates hepatic IGF-1 expression. Here we studied nucleosome occupancy and CpG methylation at a putative growth hormone-responsive element in intron 2 (in2GHRE) of the hepatic IGF-1 gene in normal, sham-operated, and IUGR mice. Nucleosome occupancy and CpG methylation were determined in embryonic stem cells (ESCs) and in liver at postnatal days 14, 21, and 42. For CpG methylation, additional time points out to 2 yr were analyzed. We confirmed the putative mouse in2GHRE was GH-responsive, and in normal mice, a single nucleosome was displaced from the hepatic in2GHRE by postnatal day 21, which exposed two STAT5b DNA binding sites. Nucleosome displacement correlated with developmentally programmed CpG demethylation. Finally, IUGR significantly altered the nucleosome-depleted region (NDR) at the in2GHRE of IGF-1 on postnatal day 21, with either complete absence of the NDR or with a shifted NDR exposing only one of two STAT5b DNA binding sites. An NDR shift was also seen in offspring of sham-operated mothers. We conclude that prenatal insult such as IUGR or anesthesia/surgery could perturb the proper formation of a well-positioned NDR at the mouse hepatic IGF-1 in2GHRE necessary for transitioning to an open chromatin state.

Mortality and glycemic control among patients with acute and chronic myeloid leukemia and diabetes: a case-control study.

AIM: We examined the association between diabetes and survival in patients with acute and chronic myeloid leukemia and the association of leukemia with glycemic control. PATIENTS & METHODS: Patients with leukemia with and without diabetes (2007-2015) were retrospectively identified and matched 1:1 (n = 70 per group). Overall survival was estimated by the Kaplan-Meier method. Hemoglobin A1c and glucose levels the year after leukemia diagnosis were compared by mixed models. RESULTS: Among 25 of 70 patients with diabetes, mean hemoglobin A1c during the year after leukemia diagnosis was 6.8%. Kaplan-Meier-estimated 3-year survival was 46% for diabetes patients versus 45% for controls (p = 0.79). CONCLUSION: No associations were found between leukemia, diabetes, survival and glycemic control.

Early postnatal nutrition and programming of the preterm neonate.

Early postnatal nutrition is a vital determinant of adult health; this is particularly true for the infant born prematurely and cared for in a hospital setting such as the neonatal intensive care unit. Human and animal studies support the contribution of postnatal dietary composition and the rate of extrauterine growth to long-term metabolic outcomes. One mechanism by which postnatal nutrition affects long-term outcome is via developmental programming. Programming, or the modulation of gene expression to impart a short-term advantage accompanied by a long-term cost, may be achieved by epigenetic modifications to chromatin. This review summarizes the details of postnatal nutritional content and rate of growth on the development of metabolic disease. The role of epigenetics in developmental programming of the preterm infant is also discussed, with an emphasis on animal models of dietary manipulation and directions in which the field must move in order to formulate effective feeding strategies for the preterm infant.