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Strawn, M.

Publications and source records attributed to Strawn, M..

2 recordsLinked to original sources

Can blood at adult age predict epigenetic changes of the brain during fetal stages?

Correspondence in DNA methylation between blood and brain is known in humans. If this pattern is present in pig has not been examined. In this study, we profiled DNA methylation of blood from pigs at adult ages, and compared those with the methylation profiles of fetal brain. Neural network regression modeling showed specific methylations in the adult blood that can reliably predict methylation of the fetal brain. Genes associated with these predictive methylations included markers of specific cell types of blood and brain, in particular, markers of bone marrow hematopoietic progenitors, and glial cells primarily the ependymal and Schwann cells of brain. The results of this study show that developmental methylation changes of the brain during fetal stages are maintained as an epigenetic memory in the blood in adult life. Thus, pig models may be harnessed to uncover potential roles of epigenetic memory in brain health and diseases.

genomics↗

Fetal origin of sex-bias brain aging

DNA methylation plays crucial roles during fetal development as well as aging. Whether the aging of the brain is programmed at the fetal stage remains untested. To test this hypothesis, mouse epigenetic clock (epiclock) was profiled in fetal (gestation day 15), postnatal (day 5), and aging (week 70) brain of male and female C57BL/6J inbred mice. Data analysis showed that on week 70 the female brain was epigenetically younger than the male brain. Predictive modeling by neural network identified specific methylations in the brain at the developing stages that were predictive of epigenetic state of the brain during aging. Transcriptomic analysis showed coordinated changes in expression of epiclock genes in the fetal brain relative to placenta. Whole-genome bisulfite sequencing identified sites that were methylated both in the placenta and fetal brain in a sex-specific manner. Epiclock genes and genes associated with specific signaling pathways, primarily the gonadotropin-releasing hormone receptor (GnRHR) pathway, were associated with these sex-bias methylations in the placenta as well as fetal brain. Transcriptional crosstalk among the epiclock and GnRHR pathway genes was evident in the placenta that was maintained in the brain during development as well as aging. Collectively, these findings suggest that sex differences in the aging of brain are of fetal origin and epigenetically linked to the placenta.

genomics↗