c-Myc is essential for hematopoietic stem cell differentiation and regulates Lin-Sca-1+c-Kit- cell generation through p21
c-Myc is essential for hematopoietic stem cell differentiation and regulates Lin-Sca-1+c-Kit- cell generation through p21
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DOI：
10.1016/j.exphem.2007.05.015
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发表时间：
2007-09-01
影响因子：
2.6
通讯作者：
de Alboran, Ignacio Moreno
中科院分区：
文献类型：
--
作者：
Baena, Esther;Ortiz, Maitane;de Alboran, Ignacio Moreno
客观的。 c-Myc 蛋白是碱性区/螺旋-环-螺旋/亮氨酸拉链 (bHLHZip) 转录因子家族的成员，参与多种细胞类型的增殖、分化和凋亡的调节。本研究的目的是表征原癌基因 c-myc 在出生后发育过程中造血干细胞 (HSC) 中的作用。材料和方法。我们生成了一个条件小鼠模型，该模型允许我们以诱导方式灭活骨髓 (BM) 中的 c-myc。结果。我们发现，BM 中 c-Myc 的条件性失活会严重损害 HSC 分化，导致淋巴和骨髓细胞数量显着减少。 BM 中的 c-Myc 缺失导致表达高水平细胞周期抑制剂 p2l 的 Lin(-)Sca-1(+)c-Kit(-) 细胞群大量积累，而其起源和功能尚不清楚。 p2l 和 c-Myc 的体内失活使 Lin(-)Sca-1(+)c-Kit(-) 细胞数量正常化并恢复正常增殖。讨论了这些细胞的潜在起源和功能。结论。 c-Myc 在 HSC 维持和分化中发挥作用，并可能通过细胞周期调节因子 p21 调节 Lin(-)Sca-1(+)c-Kit(-) 的生成 (c) 2007 ISEH 血液学和干细胞协会。由爱思唯尔公司出版
Objective. The c-Myc protein is a member of the basic region/helix-loop-helix/leucine zipper (bHLHZip) transcription factor family, which is implicated in regulation of proliferation, differentiation, and apoptosis in multiple cell types. The aim of this study was to characterize the role of the proto-oncogene c-myc in hematopoietic stem cells (HSC) during postnatal development.Material and Methods. We have generated a conditional mouse model that allows us to inactivate c-myc in bone marrow (BM) in an inducible fashion.Results. We show that conditional inactivation of c-Myc in BM severely impairs HSC differentiation, leading to a striking decrease in the number of lymphoid and myeloid cells. c-Myc deletion in BM causes substantial accumulation of a Lin(-)Sca-1(+)c-Kit(-) cell population expressing high levels of the cell-cycle inhibitor p2l, whose origin and function are otherwise poorly characterized. In vivo inactivation of p2l and c-Myc normalizes Lin(-)Sca-1(+)c-Kit(-) cell numbers and restores normal proliferation. The potential origin and function of these cells are discussed.Conclusions. c-Myc plays a role in HSC maintenance and differentiation and might be regulating generation of Lin(-)Sca-1(+)c-Kit(-) through the cell-cycle regulator p21 (c) 2007 ISEH Society for Hematology and Stem Cells. Published by Elsevier Inc.