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SCL/TAL-1基因在胚胎发育过程中于造血系统和血管系统的祖细胞中表达。

The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis.

作者信息

Kallianpur A R, Jordan J E, Brandt S J

机构信息

Department of Medicine (Hematology), Vanderbilt University Medical Center, Nashville, TN.

出版信息

Blood. 1994 Mar 1;83(5):1200-8.

PMID:8118024
Abstract

Activation of the SCL (or TAL-1) gene as a result of chromosomal translocation or deletion is a frequent molecular lesion in acute T-cell leukemia. By virtue of its membership in the basic helix-loop-helix family of transcription factors, the SCL gene is a candidate to regulate events in hematopoietic differentiation. We have used polyclonal antibody raised against a bacterial expressed malE-SCL fusion protein to characterize SCL protein expression in postimplantation embryos and in neonatal and adult mice. SCL protein was detected at day 7.5 post coitum at both embryonic and extraembryonic sites, approximately 24 hours before the formation of recognizable hematopoietic elements. Expression then localized to blood islands of the yolk sac followed by localization to fetal liver and spleen, paralleling the hematopoietic activity of these tissues during development. SCL protein was detected in erythroblasts in fetal and adult spleen, myeloid cells and megakaryocytes in spleen and bone marrow, mast cells in skin, and in rare cells in fetal and adult thymus. In addition, SCL protein was noted in endothelial progenitors in blood islands and in endothelial cells and angioblasts in a number of organs at times coincident with their vascularization. SCL expression was also observed in other nonhematopoietic cell types in the developing skeletal and nervous systems. These results show that SCL expression is one of the earliest markers of mammalian hematopoietic development and are compatible with a role for this transcription factor in terminal differentiation of the erythroid and megakaryocytic lineages. SCL expression by cells in the thymus suggests that the gene may be active at some stage of T-cell differentiation and may be relevant to its involvement by chromosomal rearrangements in T-lymphoid leukemias. Finally, expression of the gene in developing brain, cartilage, and vascular endothelium indicates SCL may have actions in neural development, osteogenesis, and vasculogenesis, as well as in hematopoietic differentiation.

摘要

由于染色体易位或缺失导致的SCL(或TAL-1)基因激活是急性T细胞白血病中常见的分子病变。凭借其在转录因子基本螺旋-环-螺旋家族中的成员身份,SCL基因是调节造血分化过程中事件的候选基因。我们使用针对细菌表达的malE-SCL融合蛋白产生的多克隆抗体来表征植入后胚胎以及新生和成年小鼠中SCL蛋白的表达。在交配后第7.5天,在胚胎和胚外部位均检测到SCL蛋白,大约在可识别的造血元件形成前24小时。随后表达定位于卵黄囊的血岛,接着定位于胎儿肝脏和脾脏,这与这些组织在发育过程中的造血活性平行。在胎儿和成年脾脏的成红细胞、脾脏和骨髓中的髓样细胞和巨核细胞、皮肤中的肥大细胞以及胎儿和成年胸腺中的罕见细胞中检测到SCL蛋白。此外,在血岛中的内皮祖细胞以及许多器官中与血管形成同时期的内皮细胞和成血管细胞中也发现了SCL蛋白。在发育中的骨骼和神经系统的其他非造血细胞类型中也观察到了SCL表达。这些结果表明,SCL表达是哺乳动物造血发育的最早标志物之一,并且与该转录因子在红系和巨核细胞系终末分化中的作用相符。胸腺细胞中SCL的表达表明该基因可能在T细胞分化的某个阶段活跃,并且可能与其在T淋巴细胞白血病中通过染色体重排的参与有关。最后,该基因在发育中的脑、软骨和血管内皮中的表达表明SCL可能在神经发育、成骨、血管生成以及造血分化中发挥作用。

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