Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity
Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity
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DOI：
10.1101/gad.1727208
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发表时间：
2008-12-01
影响因子：
10.5
通讯作者：
Oliver, Guillermo
中科院分区：
文献类型：
--
作者：
Johnson, Nicole C.;Dillard, Miriam E.;Oliver, Guillermo
同源异型盒基因Prox 1的活性对于静脉血内皮细胞（BEC）获得淋巴管内皮细胞（LEC）命运是必要的和足够的。我们确定，分化的LEC表型是一个塑料，可重编程的条件下，依赖于恒定的Prox 1活性，其维护。我们发现，在胚胎，出生后，或成人阶段的Prox 1有条件的下调是足以重编程LEC BEC。因此，突变的淋巴管的身份也被部分重编程，因为它们获得了血管系统的一些典型特征。siRNA介导的培养LEC中Prox 1的下调表明LEC重编程为BEC是一个Prox 1依赖的细胞自主过程。我们建议，Prox 1作为一个二元开关，抑制BEC身份，促进和维持LEC身份;关闭Prox 1活性足以启动一个重编程级联反应，导致LEC脱分化成BEC。因此，LEC是少数需要恒定表达某种基因以维持其表型身份的分化细胞类型之一。
The activity of the homeobox gene Prox1 is necessary and sufficient for venous blood endothelial cells (BECs) to acquire a lymphatic endothelial cell (LEC) fate. We determined that the differentiated LEC phenotype is a plastic, reprogrammable condition that depends on constant Prox1 activity for its maintenance. We show that conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages is sufficient to reprogram LECs into BECs. Consequently, the identity of the mutant lymphatic vessels is also partially reprogrammed as they acquire some features typical of the blood vasculature. siRNA-mediated down-regulation of Prox1 in LECs in culture demonstrates that reprogramming of LECs into BECs is a Prox1-dependent, cell-autonomous process. We propose that Prox1 acts as a binary switch that suppresses BEC identity and promotes and maintains LEC identity; switching off Prox1 activity is sufficient to initiate a reprogramming cascade leading to the dedifferentiation of LECs into BECs. Therefore, LECs are one of the few differentiated cell types that require constant expression of a certain gene to maintain their phenotypic identity.