Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion.
Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion.
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DOI：
10.1111/cpr.13125
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发表时间：
2021-11
影响因子：
8.5
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Du L;Deng W;Zeng S;Xu P;Huang L;Liang Y;Wang Y;Xu H;Tang J;Bi S;Zhang L;Li Y;Ren L;Lin L;Deng W;Liu M;Chen J;Wang H;Chen D
成功妊娠涉及母体蜕膜和胎儿胎盘单位之间的稳态，其破坏有助于损害妊娠结局，包括复发性自然流产（RSA）。母体蜕膜细胞异质性在RSA中的作用尚待阐明。通过无偏单细胞RNA测序（scRNA-seq）分析了从RSA患者和健康对照中分离的蜕膜样品中的共66，078个单细胞。我们的scRNA-seq结果显示，基质细胞是妊娠早期蜕膜中最丰富的细胞类型。RSA样本伴有异常蜕膜化，基质细胞与其他细胞类型之间的通讯明显受阻，如巨噬细胞和NK细胞的异常激活。此外，RSA中过度活化的TNF超家族成员12（TNFSF 12，TWEAK）和FASLG与基质细胞死亡和妊娠失败密切相关。我们的研究揭示了正常和RSA早孕蜕膜中的细胞组成和通讯，为RSA的病理学提供了有见地的信息，并为预防妊娠丢失铺平了道路。复发性自然流产（RSA）是一种复杂的妊娠并发症，其发病机制复杂，发病机制至今仍不清楚。发育中的胎儿和母体蜕膜之间的稳态对于妊娠维持至关重要。通过利用scRNA-Seq探索正常和RSA蜕膜中的细胞异质性，我们揭示了这两种不同蜕膜中细胞组成和通信的差异。我们的研究发现，基质细胞是最丰富的细胞群在蜕膜，有三个不同的亚群在不同的蜕膜化阶段和两个成纤维细胞。有两个独立的基质细胞蜕膜化的轨迹标记的PLA 2G 2A和WNT 4。作为蜕膜中最丰富的细胞群，基质细胞主导着与其他细胞类型的通讯，包括内皮细胞、巨噬细胞、uNK细胞和血管周围细胞。与正常蜕膜相比，RSA蜕膜基质细胞明显减少，巨噬细胞增多。此外，我们提出了一些以前未认识到的信号通路之间的不同类型的细胞在蜕膜，也描绘了显着改变正常和RSA蜕膜之间的通信。RSA中TWEAK和FASLG的异常激活被认为是导致间质细胞死亡和妊娠失败的潜在原因。我们的研究揭示了正常和RSA早孕蜕膜中的细胞组成和通讯，为RSA的病理学提供了有见地的信息，并将为预防妊娠丢失铺平道路。
Successful pregnancy involves the homeostasis between maternal decidua and fetoplacental units, whose disruption contributes to compromised pregnancy outcomes, including recurrent spontaneous abortion (RSA). The role of cell heterogeneity of maternal decidua in RSA is yet to be illustrated. A total of 66,078 single cells from decidua samples isolated from patients with RSA and healthy controls were analysed by unbiased single‐cell RNA sequencing (scRNA‐seq). Our scRNA‐seq results revealed that stromal cells are the most abundant cell type in decidua during early pregnancy. RSA samples are accompanied by aberrant decidualization and obviously obstructed communication between stromal cells and other cell types, such as abnormal activation of macrophages and NK cells. In addition, the over‐activated TNF superfamily member 12 (TNFSF12, TWEAK) and FASLG in RSA are closely related to stromal cell demise and pregnancy failure. Our research reveals that the cell composition and communications in normal and RSA decidua at early pregnancy and provides insightful information for the pathology of RSA and will pave the way for pregnancy loss prevention. Recurrent spontaneous abortion (RSA), characterized by pregnancy loss before 20 weeks of gestation more than twice, is an intricated pregnancy complication with enigmatic underlying mechanism ascribes to its complex pathogenesis. The homeostasis between the developing foetus and maternal decidua is critical for pregnancy maintenance. By exploring the cell heterogeneity in normal and RSA decidua utilizing scRNA‐Seq, we unravel the discrepancies in cell composition and communications in these two distinct deciduae. Our investigations uncover that stromal cells are the most abundant cell populations in the decidua, with three different subpopulations at various decidualization stages and two fibroblasts. There are two separated trajectories of stromal cell decidualization marked by PLA2G2A and WNT4. As the most abundant cell population in the decidua, the stromal cells dominate the communications with other cell types, including endothelial cells, macrophages, uNK cells and perivascular cells. Compared with normal decidua, decidualized stromal cells are overtly decreased in RSA decidua with augmented macrophages. In addition, we present some previously unappreciated signaling pathways among different cells types in decidua and also depict the remarkably changed communications between normal and RSA decidual. The aberrant activated TWEAK and FASLG in RSA are considered to be potential reasons for stromal cells demise and pregnancy failure. Our research reveals the cell composition and communications in normal and RSA decidua at early pregnancy and provides insightful information for the pathology of RSA and will pave the way for pregnancy loss prevention.
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影响因子：
2.6
作者：
Ferreira, Gustavo Dias;Capp, Edison;Germeyer, Ariane
通讯作者：
Germeyer, Ariane
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Erlebacher, Adrian
DOI：
10.1073/pnas.1706546114
发表时间：
2017-10-03
影响因子：
11.1
作者：
Garrido-Gomez, Tamara;Dominguez, Francisco;Simon, Carlos
通讯作者：
Simon, Carlos
影响因子：
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作者：
Hirota, Yasushi;Daikoku, Takiko;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.