Molecular signatures of proliferation and quiescence in hematopoietic stem cells.
Molecular signatures of proliferation and quiescence in hematopoietic stem cells.
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DOI：
10.1371/journal.pbio.0020301
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发表时间：
2004-10
期刊：
影响因子：
9.8
通讯作者：
Goodell MA
中科院分区：
文献类型：
--
作者：
Venezia TA;Merchant AA;Ramos CA;Whitehouse NL;Young AS;Shaw CA;Goodell MA
成体组织中的干细胞主要是静止的，但具有巨大的增殖能力，以实现自我更新和补充其组织成分。虽然单个造血干细胞（HSC）可以产生足够的原始后代来重新填充许多受体，但对维持其效力或调节其自我更新的分子机制知之甚少。在这里，我们研究了基因表达的变化，发生在一个时间过程中，当HSC被诱导增殖和体内恢复到静止状态。将这些数据与代表自然增殖的胎儿HSC和其静止的成人对应物之间差异的数据进行比较。生物信息学策略用于将从微阵列产生的时间排序的基因表达谱分组为静止和分裂干细胞的特征。一种用于计算我们的基因列表的基因本体分组中的统计学显著富集的新方法揭示了构成HSC行为基础的签名内的元素亚组，并允许我们建立HSC活化循环的分子模型。最初，静止的HSC表现出准备就绪的状态。增殖信号诱导准备状态，随后是可分为早期和晚期的活跃增殖。静止的重新诱导涉及在重建稳态之前迁移分子表达的变化。我们还确定了两个基因，在激活过程中增加基因和蛋白质表达，并可能代表新的标记物增殖干细胞。这些数据将是有用的，在试图概括的HSC自我更新过程中的干细胞的治疗性扩增，我们的模型可能与收购的自我更新特征的癌症干细胞。这项对造血干细胞基因表达的全面研究揭示了干细胞从静止到增殖再返回时发生的一些关键细胞变化
Stem cells resident in adult tissues are principally quiescent, yet harbor enormous capacity for proliferation to achieve self renewal and to replenish their tissue constituents. Although a single hematopoietic stem cell (HSC) can generate sufficient primitive progeny to repopulate many recipients, little is known about the molecular mechanisms that maintain their potency or regulate their self renewal. Here we have examined the gene expression changes that occur over a time course when HSCs are induced to proliferate and return to quiescence in vivo. These data were compared to data representing differences between naturally proliferating fetal HSCs and their quiescent adult counterparts. Bioinformatic strategies were used to group time-ordered gene expression profiles generated from microarrays into signatures of quiescent and dividing stem cells. A novel method for calculating statistically significant enrichments in Gene Ontology groupings for our gene lists revealed elemental subgroups within the signatures that underlie HSC behavior, and allowed us to build a molecular model of the HSC activation cycle. Initially, quiescent HSCs evince a state of readiness. The proliferative signal induces a preparative state, which is followed by active proliferation divisible into early and late phases. Re-induction of quiescence involves changes in migratory molecule expression, prior to reestablishment of homeostasis. We also identified two genes that increase in both gene and protein expression during activation, and potentially represent new markers for proliferating stem cells. These data will be of use in attempts to recapitulate the HSC self renewal process for therapeutic expansion of stem cells, and our model may correlate with acquisition of self renewal characteristics by cancer stem cells. This comprehensive study of gene expression in hematopoietic stem cells reveals some key cellular changes that occur when the stem cells transition from quiescence to proliferation and back again
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影响因子：
15.9
作者：
Levy, DE;Lee, CK
通讯作者：
Lee, CK
影响因子：
5.3
作者：
HURET, JL;TANZER, J;HENRYAMAR, M
通讯作者：
HENRYAMAR, M
DOI：
10.1073/pnas.202614899
发表时间：
2002-11-26
影响因子：
11.1
作者：
Chen, CZ;Li, M;Lodish, HF
通讯作者：
Lodish, HF
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT
影响因子：
20.3
作者：
Craddock, CF;Nakamoto, B;Papayannopoulou, T
通讯作者：
Papayannopoulou, T