Unfortunately, the authors did not Caspase-independent apoptosis investigate whether recipient rats receiving the serum from injured rats acquired adaptive characteristics of the fibrogenic component of wound healing. They next showed that conditioned media, derived from activated human hepatic stellate cells, have the ability to enhance H2A.Z distribution and H3K27me modifications in Pparg in human mesenchymal stem cells (Fig. 1). This study provides new

evidence that acquired characteristics can be transferred from somatic cells to germ cells through the serum, passing through the Weismann barrier, which strongly supports Lamarckian inheritance. This study raises many questions and further investigation MK-1775 research buy is required. The authors claim that the enrichment of H2A.Z and H3K27me3 at the Pparg locus in sperm from injured male rats were the epigenetic source for adaptation of the hepatic wound-healing response in offspring. If this consideration is true, this epigenetic information ought to spread across all cells that make up individuals in the next generation. The authors monitored the localization of H2A.Z and H3K27me3 at the Pparg locus only in sperm from injured rats and livers (at peak fibrosis) from their injured offspring. To test their hypothesis, epigenetic modifications at the Pparg locus should also be traced from sperm derived from injured rats to early embryos

and various cell types in the offspring. The authors focused on the effect of injured liver only on the adaptation to hepatic disease. However, it is possible selleck compound that the serum from injured rats may alter other types of epigenetic information, nonadaptive effects to hepatic disease in their sperm. To test this possibility, genome-wide approaches, such as chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-Seq), should be used to map the liver injury-induced global changes in epigenetic modification in sperm. Such studies may more comprehensively elucidate epigenetic and nonadaptive effects induced by liver injury. I consider that there are two important

issues in the study of epigenetic transgenerational effects. One is the identification of the “primary epigenetic marks” that are written or erased by environmental cues in germ cells; the other is the extraction of “inheritable epigenetic marks” among primary epigenetic marks beyond a given generation. Epigenetic information is established by the complex crosstalk of transcription factors, epigenetic modifiers, and signal transduction. To identify primary epigenetic marks, it is necessary to exclude secondary effects. Cultured germline stem (GS) cells, which can yield offspring, are a suitable resource with which to identify the primary epigenetic marks established by environmental conditions in germ cells.