Single-Cell Transcriptomics Analysis Showing Functional Heterogeneity in Decidual Stromal Cells during Labor

Huang, Ju; Xie, Yingming; Peng, Qiaozhen; Wang, Weinan; Pei, Chenlin; Zhao, Yanhua; Liu, Rong; Huang, Lihui; Li, Tieping; Nie, Jia; Liu, Lijuan; Zhang, Xiaowen; Luo, Xianggui; Luo, Jiefeng; Zhang, Weishe

doi:10.1136/jim-2020-001616

Cited by 3 publications

(5 citation statements)

References 34 publications

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“…The clusters most prominently influenced by labor in the CAMs were fetal stromal cells, maternal decidual cells, and maternal macrophages. The participation of decidual cells (65,(98)(99)(100)(101)(102)(103) and maternal macrophages (65,76,(104)(105)(106)(107) in the process of labor has been investigated; however, a role for fetal stromal cells in parturition is not well established. Previous studies have explored the utility of mesenchymal stromal cells (MSCs) derived from the CAM for cellular therapy applications (108,109).…”

Section: Discussionmentioning

confidence: 99%

Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing

Garcia-Flores,

Romero,

Tarca

et al. 2024

Sci. Transl. Med.

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Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor. First, a single-cell atlas of the human placenta was established, demonstrating that maternal and fetal cell types underwent changes in transcriptomic activity during labor. Cell types most affected by labor were fetal stromal and maternal decidual cells in the chorioamniotic membranes (CAMs) and maternal and fetal myeloid cells in the placenta. Cell-cell interaction analyses showed that CAM and placental cell types participated in labor-driven maternal and fetal signaling, including the collagen, C-X-C motif ligand (CXCL), tumor necrosis factor (TNF), galectin, and interleukin-6 (IL-6) pathways. Integration of scRNA-seq data with publicly available bulk transcriptomic data showed that placenta-derived scRNA-seq signatures could be monitored in the maternal circulation throughout gestation and in labor. Moreover, comparative analysis revealed that placenta-derived signatures in term labor were mirrored by those in spontaneous preterm labor and birth. Furthermore, we demonstrated that early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or prelabor ruptured membranes. Collectively, our findings provide insight into the maternal-fetal cross-talk of human parturition and suggest that placenta-derived single-cell signatures can aid in the development of noninvasive biomarkers for the prediction of preterm birth.

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Section: Discussionmentioning

confidence: 99%

Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing

Garcia-Flores,

Romero,

Tarca

et al. 2024

Sci. Transl. Med.

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“…The protocol herein was developed to allow for the isolation of high-quality single-cell suspensions from the human placental tissues, the BP + PV and CAM. While previous studies, which the current protocol builds upon, performed the digestion and isolation of cells from the BP + PV [11][12][13][14][15][16][17][18][19] , we are not aware of any established protocols for the digestion of CAM for downstream single-cell applications; thus, the inclusion of this distinct tissue represents a novel aspect of the current protocol that may benefit those researchers who are interested solely in the CAM.…”

Section: Comparison With Other Methodsmentioning

confidence: 99%

“…It is also worth mentioning that our protocol was designed for the indiscriminate isolation of cell types present in the BP + PV and CAM tissues (see 'Anticipated results'), which is an important consideration when performing unbiased high-throughput downstream analyses such as scRNAseq. A number of previous isolation protocols were developed with the aim of separating specific cell types, such as leukocytes 17,18 , decidual stromal cells 15 or trophoblast subsets 14 , or were targeted toward a specific compartment (e.g., the decidua [16][17][18] or the placenta 14,19 ). Therefore, our protocol may be best suited for researchers interested in the complete cellular landscape of the BP + PV and CAM.…”

Section: Comparison With Other Methodsmentioning

confidence: 99%

Preparation of single-cell suspensions from the human placenta

Garcia‐Flores

Pusod

et al. 2022

Nat Protoc

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Single-cell RNA-sequencing (scRNA-seq) allows the characterization of cellular composition and interactions in complex tissues. An essential prerequisite for scRNA-seq is the preparation of high-quality single-cell suspensions. So far, no protocols have been described for preparing such suspensions from the placenta, an essential organ for fetal development and a site of maternal-fetal immune interaction. Here we describe a protocol for the preparation of high-quality single-cell suspensions from human placental tissues-namely, the basal plate, placental villi and chorioamniotic membranes. The protocol outlines the collection of tissues from the placenta, tailored dissociation procedures for each tissue, and the cryopreservation of single-cell suspensions for multiplex sequencing library preparation. The protocol can be performed by a qualified investigator with basic working knowledge of placental structure. Moreover, the single-cell suspensions generated by using this protocol are compatible with droplet-based scRNA-seq technology, such as the 10x Genomics Chromium system. This protocol reliably produces single-cell suspensions from the placental tissues with high yield and viability for scRNA-seq. This protocol takes ~6 h to complete from tissue collection to cryopreservation of single-cell suspensions, and an additional 2 h for thawing of cryopreserved single cells.

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“…New evidence from scRNA-seq has also highlighted the heterogeneity of peripartum DSCs, which play multiple roles in labor. 78…”

Section: Labor Initiationmentioning

confidence: 99%

“…DSCs may maintain their heterogeneity during the perinatal period until delivery, which may have important implications for labor. New evidence from scRNA-seq has also highlighted the heterogeneity of peripartum DSCs, which play multiple roles in labor 78 …”

Section: Functions Of Dscs and Deciduamentioning

confidence: 99%

Decidualization and Related Pregnancy Complications

Tong

Yang

et al. 2021

Maternal-Fetal Medicine

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Decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal cells. Human decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming, which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate production. Decidualization extends from the primary decidual zone to the secondary decidual zone, and then exits through apoptosis. Evidences support that decidual fibroblasts function as the pool of decidual stromal cells during pregnancy. Decidualization undergoes an acute inflammatory phase, an anti-inflammatory secretory phase to the final recession phase. The decidualization of the inner layer of endometrium, termed decidua, is the most critical determinant of pregnancy success, which can promote placenta formation, modulate immune tolerance, foster resistance to oxidative stress, sense embryo quality, and control labor. Failure to adequate decidualization in terms of hormones, biochemistry, and immunology leads to adverse pregnancy outcomes, including diseases such as preeclampsia, miscarriage, premature labor, repeated implantation failures, and some age-related decline in reproductive capacity. The development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of decidualization. However, decidualization is a dynamic, multi-step process, and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be achieved. The study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.

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Single-Cell Transcriptomics Analysis Showing Functional Heterogeneity in Decidual Stromal Cells during Labor

Cited by 3 publications

References 34 publications

Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing

Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing

Preparation of single-cell suspensions from the human placenta

Decidualization and Related Pregnancy Complications

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