Imprinted X‐chromosome inactivation impacts primitive endoderm differentiation in mouse blastocysts

Imprinted X‐chromosome inactivation impacts primitive endoderm differentiation in mouse blastocysts
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DOI:
10.1002/1873-3468.13676
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发表时间:
2019-11
期刊:
影响因子:
3.5
通讯作者:
A. Fukuda;N. Motosugi;Mikiko Ando;M. Kimura;A. Umezawa;H. Akutsu
A. Fukuda;N. Motosugi;Mikiko Ando;M. Kimura;A. Umezawa;H. Akutsu
中科院分区:
生物学3区
文献类型:
--
作者:
A. Fukuda;N. Motosugi;Mikiko Ando;M. Kimura;A. Umezawa;H. Akutsu

文献摘要

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表观遗传学和转录组改变对于谱系特化至关重要,表现为雌性小鼠植入前胚胎中的印记X染色体失活(iXCI)。然而,各种因素如何影响转录组状态和谱系承诺仍不清楚。我们发现,与iXCI损失相比,体外培养持续时间强烈影响转录变异。内细胞团(ICM)的主要转录和表观基因组因子的单细胞分析显示,表达的性别特异性差异因原始内胚层(PrE)中iXCI的缺失而减少,但在上胚层中则不然。女性有较高比例的ICM相比,在男性中,和PrE的发展受到影响的iXCI状态在女性胚胎。我们的研究结果提供了深入了解性别差异和iXCI功能的谱系规范。
Epigenetic and transcriptome alterations are essential for lineage specification, represented by imprinted X‐chromosome inactivation (iXCI) in female mouse preimplantation embryos. However, how various factors affect transcriptome states and lineage commitment remains unclear. We found that in vitro culture duration strongly influences transcriptional variation compared to iXCI loss. Single‐cell analysis of the inner cell mass (ICM) for major transcription and epigenomic factors revealed that sex‐specific differences in expression are diminished by loss of iXCI in the primitive endoderm (PrE) but not in the epiblast. Females had a higher proportion of ICM compared to that in males, and PrE development was affected by iXCI states in female embryos. Our findings provide insight into sex differences and iXCI function in lineage specification.