Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Sci Rep. 2022 Nov 4;12(1):18313. doi: 10.1038/s41598-022-20781-9.
Even though the mother and the fetus of placental mammals are immunologically non-self with respect to one other, mutual exchange of small numbers of cells between them is known to occur. Maternal cells entering the fetus, called maternal microchimeric cells (MMc cells), are thought to be involved in different physiological phenomena, such as establishing immune tolerance, tissue repair, and the pathogenesis or deterioration of some inflammatory diseases and congenital malformations. While specific MMc cell types have been reported as associated with these phenomena, the contribution of MMc cells to these different outcomes remains unknown. As one possibility, we hypothesized that different embryos have differing repertoires of MMc cell types, leading to or biasing embryos toward different fates. To date, no studies have succeeded in identifying the MMc cell type repertoire of a single embryo. Accordingly, here, we isolated MMc cells from whole mouse embryos, determined their types, and analyzed their MMc cell type variability. By combining our previously established, whole-embryonic MMc isolation method with single-cell RNA sequencing, we successfully estimated the cell type repertoires of MMc cells isolated from 26 mouse embryos. The majority of MMc cells were immune-related cells, such as myeloid cells and granulocytes. We also detected stem cell-like MMc cells expressing proliferation marker genes and terminally differentiated cells. As hypothesized, we noted statistically significant inter-individual variation in the proportion of immune-related cells in the different embryos. We here successfully estimated MMc cell types in individual whole mouse embryos. The proportion of immune-related cells significantly differed among the individual embryos, suggesting that the variations are one of the potential mechanisms underlying the differing MMc-related physiological phenomena in offspring. These findings provide insight into cell-level epigenetics by maternal cells.
尽管胎盘哺乳动物的母体和胎儿彼此在免疫学上是异己的，但已知它们之间会相互交换少量的细胞。进入胎儿的母体细胞，称为母体微小嵌合体细胞（MMc 细胞），被认为参与不同的生理现象，如建立免疫耐受、组织修复以及某些炎症性疾病和先天性畸形的发病机制或恶化。虽然已经报道了特定的 MMc 细胞类型与这些现象有关，但 MMc 细胞对这些不同结果的贡献仍不清楚。作为一种可能性，我们假设不同的胚胎具有不同的 MMc 细胞类型谱，导致或偏向胚胎走向不同的命运。迄今为止，尚无研究成功鉴定单个胚胎的 MMc 细胞类型谱。因此，在这里，我们从整个小鼠胚胎中分离出 MMc 细胞，确定其类型，并分析它们的 MMc 细胞类型变异性。通过将我们之前建立的全胚胎 MMc 分离方法与单细胞 RNA 测序相结合，我们成功地估计了从 26 个小鼠胚胎中分离出的 MMc 细胞的细胞类型谱。大多数 MMc 细胞是免疫相关细胞，如髓样细胞和粒细胞。我们还检测到表达增殖标记基因的干细胞样 MMc 细胞和终末分化细胞。正如假设的那样，我们注意到不同胚胎中免疫相关细胞的比例存在统计学上的显著个体间变异。我们在这里成功地估计了个体全小鼠胚胎中的 MMc 细胞类型。不同胚胎之间免疫相关细胞的比例存在显著差异，这表明这种变异是母体细胞介导的不同 MMc 相关生理现象的潜在机制之一。这些发现为母细胞的细胞水平表观遗传学提供了新的认识。
