Hematopoietic fingerprints: an expression database of stem cells and their progeny.
Hematopoietic fingerprints: an expression database of stem cells and their progeny.
复制标题
DOI：
10.1016/j.stem.2007.10.003
复制
发表时间：
2007-11-01
期刊：
影响因子：
23.9
通讯作者：
Goodell, Margaret A
中科院分区：
文献类型：
--
作者：
Chambers, Stuart M;Boles, Nathan C;Goodell, Margaret A
造血干细胞(HSCs)能持续再生血液系统，但目前对这一过程的调控基因还很少。为了确定参与分化和自我更新的候选因素，我们建立了一个造血干细胞及其分化后代的表达数据库，包括红细胞、粒细胞、单核细胞、NK细胞、活化和初始T细胞以及B细胞。生物信息学分析表明，HSCs的转录活性高于其后代，并且与T细胞具有共同的激活机制。每种细胞类型在特定遗传途径的调控中也表现出独特的偏向，Wnt信号在HSCs中尤其增强。我们鉴定了大约100-400个在每种细胞类型中唯一表达的基因，称为谱系“指纹”。在过度表达研究中，其中两个基因，来自NK细胞谱系的ZFP 105和来自单核细胞谱系的Ets2，能够显著影响向各自谱系的分化，证明了指纹用于识别调节分化的基因的有效性。
Hematopoietic stem cells (HSCs) continuously regenerate the hematologic system, yet few genes regulating this process have been defined. To identify candidate factors involved in differentiation and self-renewal, we have generated an expression database of hematopoietic stem cells and their differentiated progeny, including erythrocytes, granulocytes, monocytes, NK cells, activated and naive T cells, and B cells. Bioinformatic analysis revealed HSCs were more transcriptionally active than their progeny and shared a common activation mechanism with T cells. Each cell type also displayed unique biases in the regulation of particular genetic pathways, with Wnt signaling particularly enhanced in HSCs. We identified approximately 100-400 genes uniquely expressed in each cell type, termed lineage "fingerprints." In overexpression studies, two of these genes, Zfp 105 from the NK cell lineage, and Ets2 from the monocyte lineage, were able to significantly influence differentiation toward their respective lineages, demonstrating the utility of the fingerprints for identifying genes that regulate differentiation.