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Adult bone marrow-derived progenitors give rise to decidual cells and are essential for implantation and pregnancy maintenance

ABSTRACT: Bone marrow (BM)-derived progenitor cells (BMDPCs) are known to migrate and give rise to endometrial cells however their functional contribution to implantation and pregnancy are unknown . Here we show that implantation and pregnancy are strong stimuli for BMDPCs recruitment to the uterine decidua where BMDPCs differentiate into functional non-hematopoietic prolactin-producing decidual cells. Transcriptome analysis of implantation sites demonstrated that Hoxa11+/- mice transplanted with WT BM clustered hierarchically more closely with normal WT mice than with control Hoxa11+/- mice, showing normalized expression of numerous implantation-related genes. These findings reveal that BMDPCs have a major non-hematopoietic physiologic contribution to the decidual stroma, and thereby play an essential and previously unproven role in the establishment and maintenance of pregnancy.

ORGANISM(S): Mus musculus

PROVIDER: GSE93743 | GEO | 2020/01/17

REPOSITORIES: GEO

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Bone marrow-derived progenitors become decidual cells and are essential for implantation and pregnancy maintenance

Project description:The pregnant decidua is infiltrated by many immune cells which are thought to originate in the bone marrow (BM) promoting pregnancy. In addition, BM-derived progenitor cells (BMDPCs) become non-hematopoietic endometrial cells. However, whether BMDPCs become non-immune decidual cells and their functional contribution to pregnancy were previously unknown. Here, we show that embryo implantation stimulates vast BMDPCs recruitment to decidua, where BMDPCs differentiate into non-hematopoietic stromal decidual cells. In addition, to determine the functional importance of BMDPCs to pregnancy, we used mice with endometrial stromal-specific defects precluding successful pregnancy. BM transplant (BMT) from wild-type (WT) into Hoxa11-/- mice, which lack decidualization, results in uterine transcriptional changes leading to stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. By contrast, BMT from Hoxa11-/- into WT mice induces pregnancy loss. Importantly, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that BMDPCs have a novel non-hematopoietic physiologic contribution to decidual stroma, thereby playing indispensable roles in pregnancy establishment and maintenance.

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EGAS00001004069-sc-2023-02-08T16:08:31Z - samples

Project description:This dataset is part of a study that aims to provide a spatially resolved single-cell multiomics map of human trophoblast differentiation in early pregnancy. This dataset contains 10x multiome snRNA-seq/snATAC-seq from human implantation sites, decidual and placental samples from 8-9 PCW.

| EGAD00001010038 | EGA

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