Gene expression analysis of purified hematopoietic stem cells and committed progenitors
Gene expression analysis of purified hematopoietic stem cells and committed progenitors
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DOI：
10.1182/blood-2002-08-2509
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发表时间：
2003-07-01
期刊：
影响因子：
20.3
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Terskikh, AV;Miyamoto, T;Weissman, IL
终生自我更新是成体干细胞的独特特性。最近，在小鼠骨髓中发现了几种原始的多能但定向（非自我更新）造血祖细胞群。我们使用 Atlas cDNA 阵列对高度纯化的造血干细胞 (HSC) 和 6 个密切相关的祖细胞群中 1200 个选定的小鼠基因的表达进行了表征：共同骨髓祖细胞 (CMP)、粒细胞-巨噬细胞祖细胞 (GMP)、巨核细胞-红细胞祖细胞 (MEP)、共同淋巴祖细胞 (CLP) 以及 pro-T 和 pro-B细胞。聚类分析显示，近一半的差异表达转录本与 HSC 相关，支持了 HSC 活跃转录状态的概念。 HSC 簇中富含的基因包含许多发育调控基因，其中一些先前与 HSC 自我更新相关。相比之下，定向祖细胞中富集的基因大多与造血分化、免疫调节和代谢有关。因此，从 HSC 向定型祖细胞的转变与大量 HSC 相关基因的下调和有限数量的谱系特异性基因的逐步上调相关。这些遗传分析揭示了与 HSC 与下游祖细胞相关的转录本之间的定量和定性差异，并产生了可能参与 HSC 自我更新的候选基因列表。 (C) 2003 年，美国血液学会。
Lifelong self-renewal is a unique property of somatic stem cells. Recently, several primitive multipotent yet committed (non-self-renewing) hematopoietic progenitor populations were identified in mouse bone marrow. We have characterized the expression of 1200 selected mouse genes using the Atlas cDNA array in highly purified hematopoietic stem cells (HSCs) and 6 closely related progenitor populations: common myeloid progenitors (CMPs), granulocyte-macrophage progenitors (GMPs), megakaryocyte-erythtocyte progenitors (MEPs), common lymphoid progenitors (CLPs), and pro-T and pro-B cells. Cluster analysis revealed that nearly half of all differentially expressed transcripts are associated with HSCs, supporting the notion of an active transcriptional status of HSCs. Genes found enriched in the HSC cluster encompass many developmentally regulated genes, some previously associated with HSC self-renewal. In contrast, genes that are enriched in committed progenitors are mostly associated with hematopoietic differentiation, immune regulation, and metabolism. Thus, the transition from HSCs toward committed progenitors correlates with the down-regulation of a large number of HSC-associated genes and progressive up-regulation of a limited number of lineage-specific genes. These genetic analyses revealed both quantitative and qualitative differences between the transcripts associated with HSCs versus downstream progenitors and produced a list of the candidate genes, potentially involved in HSC self-renewal. (C) 2003 by The American Society of Hematology.