Uncoupling of transcriptomic and cytological differentiation in mouse spermatocytes with impaired meiosis
Uncoupling of transcriptomic and cytological differentiation in mouse spermatocytes with impaired meiosis
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DOI：
10.1091/mbc.e18-10-0681
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发表时间：
2019-03-01
影响因子：
3.3
通讯作者：
Carter, Gregory W.
中科院分区：
文献类型：
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作者：
Fine, Alexander D.;Ball, Robyn L.;Carter, Gregory W.
细胞分化是由基因表达的变化驱动的，表现为细胞表型或功能的变化。人们普遍认为，源于基因突变或其他扰动的细胞表型改变与转录组的变化直接对应，反之亦然。在这里，我们利用细胞学上明确的 Prdm9 突变小鼠作为发育停滞模型来测试细胞分化和基因表达的平行程序是否紧密协调或可以分离。通过比较野生型和突变型精母细胞的细胞学表型标记和转录组，我们鉴定了 Prdm9(-/-) 突变体中细胞和分子解偶联的多个实例。最值得注意的是，尽管 Prdm9(-/-) 生殖细胞在细线期晚期/受精卵阶段经历细胞学停滞，但它们仍然发展出后期发育亚阶段特征的基因表达特征。这些发现表明，转录组变化可能无法可靠地映射到发育扰动系统中的细胞表型。
Cell differentiation is driven by changes in gene expression that manifest as changes in cellular phenotype or function. Altered cellular phenotypes, stemming from genetic mutations or other perturbations, are widely assumed to directly correspond to changes in the transcriptome and vice versa. Here, we exploited the cytologically well-defined Prdm9 mutant mouse as a model of developmental arrest to test whether parallel programs of cellular differentiation and gene expression are tightly coordinated, or can be disassociated. By comparing cytological phenotype markers and transcriptomes in wild-type and mutant spermatocytes, we identified multiple instances of cellular and molecular uncoupling in Prdm9(-/-) mutants. Most notably, although Prdm9(-/-) germ cells undergo cytological arrest in a late-leptotene/zygotene stage, they nevertheless develop gene expression signatures characteristic of later developmental substages. These findings suggest that transcriptomic changes may not reliably map to cellular phenotypes in developmentally perturbed systems.