Abstract
During mammalian hemoglobin ontogeny, synthesis of the earliest globin chains (embryonic) is ultimately replaced by synthesis of globin chains (adult) characteristic of the fully formed organism. Elements of control of initiation, progression, and completion of globin-chain ontogeny are poorly understood. In search of a cell culture system in which ontogeny might be studied under closely controlled experimental conditions, we chose erythroid cells of the hamster embryo. First, the ontogeny of globin chains was defined in these yolk-sac-derived erythroid cells from day 10 through day 13 in gestation. Amounts of individual embryonic and adult globin chains were quantified, as were their rates of synthesis. Next, analogous studies were performed on yolk-sac erythroid cells from day 10 in gestation (prior to the appearance of fetal liver) grown in culture for 3 days, corresponding to days 10-13 in vivo. The ontogenic program in culture was virtually identical to that in vivo. Approximately 70% of active globin synthesis was embryonic at day 10 in gestation (day 0 of culture), declining to 30% by day 13 in gestation (day 3 of culture). Whereas only trace synthesis of the adult non-alpha chains (beta major and beta minor) were initially observed, their combined active synthesis achieved a level of approximately 30% 3 days later both in vivo and in culture. Cell hemoglobin content and cell morphology were similar in both systems. We conclude that an ontogenic program for globin-chain synthesis exists in these primitive erythroid cells, overriding possible influences of cell environment. Further, we suggest that these cells in culture provide a means of examining cell mechanisms associated with globin-gene ontogeny under controlled experimental conditions.
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