Benmimoun Billel, Polesello Cédric, Haenlin Marc, Waltzer Lucas
Université de Toulouse, Université Paul Sabatier (UPS), Centre de Biologie du Développement, Bâtiment 4R3, F-31062 Toulouse, France; CNRS, Centre de Biologie du Développement, UMR 5547, F-31062 Toulouse, France.
Université de Toulouse, Université Paul Sabatier (UPS), Centre de Biologie du Développement, Bâtiment 4R3, F-31062 Toulouse, France; CNRS, Centre de Biologie du Développement, UMR 5547, F-31062 Toulouse, France
Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9052-7. doi: 10.1073/pnas.1423967112. Epub 2015 Jul 6.
The maintenance of stem or progenitor cell fate relies on intrinsic factors as well as local cues from the cellular microenvironment and systemic signaling. In the lymph gland, an hematopoietic organ in Drosophila larva, a group of cells called the Posterior Signaling Centre (PSC), whose specification depends on the EBF transcription factor Collier (Col) and the HOX factor Antennapedia (Antp), has been proposed to form a niche required to maintain the pool of hematopoietic progenitors (prohemocytes). In contrast with this model, we show here that genetic ablation of the PSC does not cause an increase in blood cell differentiation or a loss of blood cell progenitors. Furthermore, although both col and Antp mutant larvae are devoid of PSC, the massive prohemocyte differentiation observed in col mutant is not phenocopied in Antp mutant. Interestingly, beside its expression in the PSC, Col is also expressed at low levels in prohemocytes and we show that this expression persists in PSC-ablated and Antp mutant larvae. Moreover, targeted knockdown and rescue experiments indicate that Col expression is required in the prohemocytes to prevent their differentiation. Together, our findings show that the PSC is dispensable for blood cell progenitor maintenance and reveal the key role of the conserved transcription factor Col as an intrinsic regulator of hematopoietic progenitor fate.
干细胞或祖细胞命运的维持依赖于内在因素以及来自细胞微环境的局部信号和全身信号传导。在果蝇幼虫的造血器官淋巴腺中,一组被称为后部信号中心(PSC)的细胞,其特化依赖于EBF转录因子Collier(Col)和HOX因子触角足(Antp),有人提出它们形成了维持造血祖细胞(前血细胞)池所需的微环境。与该模型相反,我们在此表明,PSC的基因消融不会导致血细胞分化增加或血细胞祖细胞丢失。此外,尽管col和Antp突变体幼虫都没有PSC,但在col突变体中观察到的大量前血细胞分化在Antp突变体中并未出现。有趣的是,除了在PSC中表达外,Col在前血细胞中也有低水平表达;我们还表明,这种表达在PSC消融和Antp突变体幼虫中持续存在。此外,靶向敲低和拯救实验表明前血细胞中需要Col表达以防止其分化。总之,我们的研究结果表明PSC对于血细胞祖细胞的维持是可有可无的,并揭示了保守转录因子Col作为造血祖细胞命运内在调节因子的关键作用。