Our goal is acquisition of basic information on the cell biology of mammalian hemoglobin ontogeny. A clinical goal is to utilize this information in ultimately divising attempts to ameliorate certain human hemoglobinopathies by manipulating ontogenic mechanisms. During ontogeny, synthesis of embryonic globin chains is replaced by synthesis of adult globin chains. Although earlier investigators relegated synthesis of embryonic globin to yolk-sac erythroid cells and synthesis of adult globin to ontogenically later sites (liver, spleen, bone marrow), recent work has established co-synthesis of embryonic and adult globins in yolk-sac erythroid cells of hamster, mouse, and human. Our studies will use hamster as the primary source of cells, but will utilize mouse for comparative purposes. Assays of globin-chain synthesis in hamster yolk-sac erythroid cells show that globin ontogeny (embryonic to adult) is nearly completed during the time span (approximately six days) in which the only circulating erythroid cell is derived from the yolk-sac. These actively replicating primitive erythroid cells from colonies in culture, and changes in chain synthesis in culture closely resemble the ontogeny of chain synthesis in vivo. We intend to utilize this physiologic cell system in approaching our two specific aims.
Our first aim i s to determine the extent to which an apparent pre-programming of the globin-chain ontogenic process can be diverted. We shall be assaying effects of diverse environmental influences: hormones, conditioned media, and certain non-physiologic chemical agents, all reported to affect globin-gene expression in other cell systems. The second specific aim is to search for cell mechanisms underlying our observation that colony growth and globin-chain ontogeny can proceed in culture only when both erythropoietin and thyroid hormone are present. With these aims as introductory probes into mechanisms, we anticipate that the ability to exercise tight experimental control in culture will facilitate useful interpretation of results.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Hematology Subcommittee 2 (HEM)
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St. Luke's Roosevelt Hosp Center (New York)
New York
United States
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Boussios, T; Lee, K M; Li, H et al. (1993) Expression of adult globin mRNAs in hamster yolk-sac erythroid cells during ontogeny. Exp Hematol 21:901-6
Li, H; Subar, M; Lee, K M et al. (1992) Cloning and sequence analysis of two embryonic beta-like globin cDNAs (y and z) of hamster. Biochim Biophys Acta 1130:218-20
Lee, K M; Subar, M; Li, H et al. (1992) Cloning of two adult hamster globin cDNAs (alpha and beta major). Biochim Biophys Acta 1130:343-4
Lee, K M; Bertles, J F; Boussios, T (1991) Translational control of globin chain ontogeny in hamster yolk sac erythroid cells. J Biol Chem 266:20555-60
Boussios, T; Bertles, J F; Goldwasser, E (1989) Erythropoietin. Receptor characteristics during the ontogeny of hamster yolk sac erythroid cells. J Biol Chem 264:16017-21
Boussios, T; Bertles, J F (1988) The globin gene expression program in the hamster embryo. Exp Hematol 16:1-4
Boussios, T; Bertles, J F (1987) Receptors specific for erythropoietin on yolk-sac erythroid cells. Prog Clin Biol Res 251:35-41