Research Center for Natural Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; McDonnell Genome Institute, St. Louis, MO, USA.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
HGG Adv. 2024 Jul 18;5(3):100301. doi: 10.1016/j.xhgg.2024.100301. Epub 2024 May 21.
While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.
虽然大多数异卵双胞胎有双绒毛膜胎盘，但也有罕见的报道称异卵双胞胎有单绒毛膜胎盘。异卵双胞胎的单绒毛膜胎盘允许胚胎细胞在子宫内交换，从而导致双胞胎的嵌合体现象。实际上，这种嵌合体是在混合 ABO 血型或存在性染色体不一致的细胞时偶然发现的。在这里，我们应用全基因组测序技术对一个三胞胎和一个双胞胎家庭进行了研究，使用数百万个基因组变异作为合子起源的条形码，以精确了解他们的合子组成。外周血显示来自两个姐妹合子的不对称贡献，其中一个合子是双胞胎中的主要克隆。外周血细胞的单细胞 RNA 测序进一步显示了两个姐妹合子在不同血细胞类型中的不同贡献。相比之下，口腔组织的遗传组成是纯合的，这表明宫内细胞交换仅限于血液组织。我们的研究说明了人类发育过程中双胞胎的细胞历史，这对于基因组医学时代管理嵌合体个体的健康至关重要。
