Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita, Japan.
Biol Reprod. 2010 Apr;82(4):687-97. doi: 10.1095/biolreprod.108.075697. Epub 2009 Dec 16.
During the preimplantation development of mouse embryos between the 4-cell to 8-cell stage and the morula stage, when the first irreversible segregation of cell fates proceeds into the pluripotent inner cell mass (progenitor cells to form the fetus) and the trophectoderm (to form the placenta) of blastocysts, pluripotency-maintaining and differentiation-inducing genes are expressed to coordinately regulate cell fates. Three structurally related cDNAs (Crxos1, Crxos1 sv2, and Crxos1 tv3) that exhibited concomitant elevated expression during this critical period were identified by subtractive cDNA cloning. CRXOS1 contains two homeodomains, while CRXOS1 sv2 and CRXOS1 tv3 each contain one of the homeodomains included in CRXOS1. Crxos1, Crxos1 sv2, and Crxos1 tv3 were expressed differentially during in vitro embryonic stem (ES) cell differentiation. Even under differentiation-inducing conditions, forced expression of Crxos1 sv2 inhibited the differentiation of ES cells. In contrast, under conditions that promote self-renewal of ES cells, forced expression of Crxos1 induced differentiation. Forced expression of Crxos1 resulted in induction of Gata4 but in repression of T, probably indicating that Crxos1 promotes the differentiation of ES cells into primitive endoderm, while inhibiting differentiation into mesoderm. On the other hand, no apparent effects of forced expression of Crxos1 tv3 were observed. Taken together, it was concluded that these transcripts encoding homeoproteins are capable of regulating the maintenance and/or differentiation of mouse ES cells and likely regulate that of preimplantation embryos.
在小鼠胚胎的 4 细胞至 8 细胞期和桑椹胚期之间的着床前发育过程中，当第一个细胞命运的不可逆分离进行到多能内细胞团（祖细胞形成胎儿）和滋养外胚层（形成胎盘）的胚泡时，维持多能性和诱导分化的基因被表达以协调调节细胞命运。通过减法 cDNA 克隆鉴定了三个结构相关的 cDNA（Crxos1、Crxos1 sv2 和 Crxos1 tv3），它们在这个关键时期表现出同时升高的表达。CRXOS1 包含两个同源结构域，而 CRXOS1 sv2 和 CRXOS1 tv3 每个都包含 CRXOS1 中包含的一个同源结构域。Crxos1、Crxos1 sv2 和 Crxos1 tv3 在体外胚胎干细胞（ES）细胞分化过程中表现出不同的表达。即使在诱导分化的条件下，Crxos1 sv2 的强制表达也抑制了 ES 细胞的分化。相反，在促进 ES 细胞自我更新的条件下，Crxos1 的强制表达诱导分化。Crxos1 的强制表达导致 Gata4 的诱导，但 T 的抑制，这可能表明 Crxos1 促进 ES 细胞向原始内胚层分化，同时抑制向中胚层分化。另一方面，没有观察到 Crxos1 tv3 强制表达的明显影响。综上所述，可以得出结论，这些编码同源结构域蛋白的转录本能够调节小鼠 ES 细胞的维持和/或分化，并可能调节着床前胚胎的分化。
