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首页> 外文期刊>Molecular and Cellular Biology >The Ets-related transcription factor PU.1 immortalizes erythroblasts.
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The Ets-related transcription factor PU.1 immortalizes erythroblasts.

机译：与Ets相关的转录因子PU.1使成红细胞永生。

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摘要

In vivo studies of Friend virus erythroleukemia have implied that proviral integrations adjacent to the gene for the Ets-related transcription factor PU.1 may inhibit the commitment of erythroblasts to differentiate and cause their capability for indefinite transplantation (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 62:4129-4135, 1988; R. Paul, S. Schuetze, S. L. Kozak, C. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test this hypothesis, we ligated PU.1 cDNA into a retroviral vector and studied its effects on cultured cells. Infection of fibroblasts with PU.1-encoding retrovirus resulted in PU.1 synthesis followed by nuclear pyknosis, cell rounding, and degeneration. In contrast, in long-term bone marrow cultures, erythroblasts were efficiently and rapidly immortalized. The resulting cell lines were polyclonal populations that contained PU.1, were morphologically blast-like, required erythropoietin and bone marrow stromal cells for survival and proliferation, and spontaneously differentiated at low frequency to synthesize hemoglobin. After 9 months in culture, erythroblasts became stroma independent, and they then grew as clonal cell lines. We conclude that PU.1 perturbs the pathway(s) that controls potential for indefinite proliferation and that it can be used to generate permanent erythroblast cell lines.
机译：对Friend病毒性红白血病的体内研究表明，与Ets相关转录因子PU.1的基因相邻的前病毒整合可能会抑制成红细胞分化并导致其无限期移植的能力（C. Spiro，B. Gliniak，和D.Kabat，J.Virol.62：4129-4135，1988; R.Paul，S.Schuetze，SL Kozak，C.Kozak和D.Kabat，J.Virol.65：464-467，1991）。为了验证这一假设，我们将PU.1 cDNA连接到了逆转录病毒载体中，并研究了其对培养细胞的作用。用编码PU.1的逆转录病毒感染成纤维细胞导致PU.1合成，随后发生核固缩，细胞变圆和变性。相比之下，在长期的骨髓培养中，成红细胞可以快速有效地永生。产生的细胞系是含有PU.1的多克隆种群，形态上呈胚细胞样，需要促红细胞生成素和骨髓基质细胞才能存活和增殖，并以低频自发分化以合成血红蛋白。培养9个月后，成红细胞变成不依赖基质的细胞，然后以克隆细胞系的形式生长。我们得出的结论是，PU.1干扰了控制无限增殖潜能的途径，可用于生成永久性成红细胞细胞系。

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