Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing
Abstract 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 i...
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Nature Portfolio
2022-11-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-022-20781-9 |
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author | Kana Fujimoto Akira Nakajima Shohei Hori Yumiko Tanaka Yoshitaka Shirasaki Sotaro Uemura Naoki Irie |
author_facet | Kana Fujimoto Akira Nakajima Shohei Hori Yumiko Tanaka Yoshitaka Shirasaki Sotaro Uemura Naoki Irie |
author_sort | Kana Fujimoto |
collection | DOAJ |
description | Abstract 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. |
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spelling | doaj.art-dc6da09bfe594a5da61d3e1850ace7912022-12-22T03:40:02ZengNature PortfolioScientific Reports2045-23222022-11-0112111410.1038/s41598-022-20781-9Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencingKana Fujimoto0Akira Nakajima1Shohei Hori2Yumiko Tanaka3Yoshitaka Shirasaki4Sotaro Uemura5Naoki Irie6Department of Biological Sciences, Graduate School of Science, University of TokyoGraduate School of Pharmaceutical Sciences, University of TokyoGraduate School of Pharmaceutical Sciences, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoGraduate School of Pharmaceutical Sciences, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoDepartment of Biological Sciences, Graduate School of Science, University of TokyoAbstract 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.https://doi.org/10.1038/s41598-022-20781-9 |
spellingShingle | Kana Fujimoto Akira Nakajima Shohei Hori Yumiko Tanaka Yoshitaka Shirasaki Sotaro Uemura Naoki Irie Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing Scientific Reports |
title | Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing |
title_full | Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing |
title_fullStr | Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing |
title_full_unstemmed | Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing |
title_short | Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing |
title_sort | whole embryonic identification of maternal microchimeric cell types in mouse using single cell rna sequencing |
url | https://doi.org/10.1038/s41598-022-20781-9 |
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