Induction of a hemogenic program in mouse fibroblasts.-猫眼课题宝

DOI：

10.1016/j.stem.2013.05.024

发表时间：

2013-08-01

期刊：

CELL STEM CELL

影响因子：

23.9

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Pereira, Carlos-Filipe;Chang, Betty;Qiu, Jiajing;Niu, Xiaohong;Papatsenko, Dmitri;Hendry, Caroline E.;Clark, Neil R.;Nomura-Kitabayashi, Aya;Kovacic, Jason C.;Ma'ayan, Avi;Schaniel, Christoph;Lemischka, Ihor R.;Moore, Kateri

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735774/?report=classic

胚胎发生期间通过内皮细胞向造血细胞的转变出现确定的造血。我们试图通过筛选一组生血活性因子来诱导小鼠成纤维细胞的这一过程。我们鉴定了四种转录因子Gata 2、Gfi 1b、cFos和Etv 6的组合，其有效地诱导内皮样前体细胞，随后出现造血细胞。前体细胞在一个整体内皮转录程序中表达人CD 34报告基因Sca 1和Prominin 1。新生造血细胞具有新生/特定造血干细胞基因表达谱和细胞表面表型。在转基因沉默和再聚集培养后，特定细胞在体外产生造血集落。因此，我们已经表明，转录因子的简单组合足以在体外诱导复杂的、动态的和多步骤的发育程序。这些发现提供了对确定性造血的规范的见解，并为未来开发患者特异性干/祖细胞以及更分化的血液制品提供了平台。

Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6 that efficiently induces endothelial-like precursor cells with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1 and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent/specifying hematopoietic stem cell gene expression profiles and cell surface phenotypes. After transgene silencing and reaggreagtion culture the specified cells generate hematopoietic colonies in vitro. Thus, we have shown that a simple combination of transcription factors is sufficient to induce a complex, dynamic and multi-step developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem/progenitor cells as well as more differentiated blood products.