Departments of Developmental Biology, Genetics, and Bioengineering, University School of Medicine , Stanford, CA 94305-5101 , USA.
Biol Open. 2013 Feb 15;2(2):121-31. doi: 10.1242/bio.20122949. Epub 2012 Nov 19.
During preimplantation development, the embryo must establish totipotency and enact the earliest differentiation choices, processes that involve extensive chromatin modification. To identify novel developmental regulators, we screened for genes that are preferentially transcribed in the pluripotent inner cell mass (ICM) of the mouse blastocyst. Genes that encode chromatin remodeling factors were prominently represented in the ICM, including Chd1l, a member of the Snf2 gene family. Chd1l is developmentally regulated and expressed in embryonic stem (ES) cells, but its role in development has not been investigated. Here we show that inhibiting Chd1l protein production by microinjection of antisense morpholinos causes arrest prior to the blastocyst stage. Despite this important function in vivo, Chd1l is non-essential for cultured ES cell survival, pluripotency, or differentiation, suggesting that Chd1l is vital for events in embryos that are distinct from events in ES cells. Our data reveal a novel role for the chromatin remodeling factor Chd1l in the earliest cell divisions of mammalian development.
在胚胎植入前发育过程中，胚胎必须建立全能性并执行最早的分化选择，这些过程涉及广泛的染色质修饰。为了鉴定新的发育调节剂，我们筛选了在小鼠囊胚多能性内细胞团（ICM）中优先转录的基因。编码染色质重塑因子的基因在 ICM 中显著表达，包括 Snf2 基因家族的成员 Chd1l。Chd1l 在胚胎干细胞（ES 细胞）中受到发育调控和表达，但它在发育中的作用尚未被研究。在这里，我们表明通过注射反义形态发生素来抑制 Chd1l 蛋白的产生会导致胚胎停滞在囊胚阶段之前。尽管在体内具有重要功能，但 Chd1l 对于培养的 ES 细胞的存活、多能性或分化并非必需，这表明 Chd1l 对于胚胎中的事件是至关重要的，而这些事件与 ES 细胞中的事件不同。我们的数据揭示了染色质重塑因子 Chd1l 在哺乳动物发育最早的细胞分裂中的新作用。
