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The liver contains diploid and polyploid hepatocytes (tetraploid, octaploid, etc.), with polyploids comprising ≥90% of the hepatocyte population in adult mice. Moreover, polyploid hepatocytes form multipolar spindles in mitosis, leading to individual chromosome gains and/or losses and random aneuploidy. The molecular mechanisms that regulate polyploidization have been well-characterized; however, it is unclear if diploid and polyploid hepatocytes function similarly in multiple contexts. The effect of aneuploidy on liver function is also unknown and the degree of liver aneuploidy is debated, with reports showing aneuploidy affects 5-60% of hepatocytes. We used mice lacking E2f7 and E2f8 in the liver (LKO), which have a polyploidization defect. We found diploid hepatocytes were enriched 20-fold in LKO livers and nearly all LKO hepatocytes were euploid compared to control hepatocytes, which were mostly aneuploid, suggesting polyploids are required for production of aneuploid progeny. Livers from LKO mice maintained normal function but became highly tumorigenic when challenged with tumor-promoting stimuli, suggesting that tumors in LKO mice were driven, at least in part, by diploid hepatocytes capable of rapid proliferation. Indeed, LKO hepatocytes were more proliferative and out-competed control hepatocytes in competitive repopulation studies. To eliminate potentially confounding effects associated with E2f7/E2f8 deficiency, diploid and polyploid hepatocytes from wild-type mice were examined. The wild-type diploid cells also showed a proliferative advantage, entering and progressing through the cell cycle faster than polyploid cells, both in vitro and during liver regeneration. Finally, to investigate the role of diploids and polyploids in chronic injury we bred LKO mice onto a tyrosinemia background, a disease model where the liver can develop disease-resistant, regenerative nodules. Survival was significantly reduced in tyrosinemic LKO mice, compared to controls, but they maintained the ability to form regenerative nodules. Molecular analyses revealed that the nodules in the tyrosinemic livers were generated via aneuploidy and inactivating mutations. In summary we identified diverse, context-specific roles for diploids and polyploids in liver function, demonstrating diploid hepatocytes are the most proliferative and have the highest capacity for liver regeneration, and polyploid hepatocytes are required for the formation of aneuploid progeny and facilitate adaptation to chronic liver disease.

Haitian Vodou is a syncretic religion that combines elements of West African beliefs and indigenous Taíno culture with a rigid framework of forced Catholicism. Western cultures have always been fascinated by, yet fearful of, Vodou and commonly depict it as devil-worship and witchcraft. It is in large part due to this pervasive view of Vodou in Haiti, as well as the challenging conditions that come with working in Haiti, that little academic interest has been paid to the nuances of the modern practice of Vodou, particularly the use of caves. In this dissertation, I incorporate ethnographic and archaeological methods to present the first comprehensive study of how modern Vodou practitioners across Haiti have incorporated caves into their syncretic ritual repertoire.Through interviews, observation, participation, and an assessment of the ephemeral material remains left behind by Vodou practitioners, I describe what forms and purposes these rituals take, determine which parts of caves are associated with different aspects of Vodou, and compare the demographics of cave practitioners to those of Vodou practitioners in general. I argue that while Vodou, as it is practiced in public and at home, follows the definitions of religion, the aspects of Vodou as it is practiced in caves are more in line with definitions of magic, and I propose three reasons for this. This research has two purposes. First, it is an ethno-archaeological study intended to fill in gaps in the academic body of work regarding Vodou in Haiti where cave usage has been ignored. As ethnography, it has the potential to inform not just academics, but a broader audience, and to correct misconceptions regarding Vodou in particular and Haiti in general. Second, this project may be of use to archaeologists, particularly those who work in caves or other ritual spaces, whose data may be influenced by the activities of past caretakers. Every cave that in this study had some form of active caretaker and the model of caretaker presented in this study may be of use in interpreting archaeological sites that share a similar economic and social structure to modern Haiti.