PBX1 expression in uterine natural killer cells drives fetal growth

Zhou, Yonggang; Fu, Binqing; Xu, Xiuxiu; Zhang, Jinghe; Tong, Xianhong; Wang, Yanshi; Dong, Zhongjun; Zhang, Xiaoren; Shen, Nan; Zhai, Yiwen; Kong, Xiangdong; Sun, Rui; Tian, Zhigang; Wei, Haiming

doi:10.1126/scitranslmed.aax1798

Cited by 64 publications

(54 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we present single-cell transcriptomes of the decidual immune microenvironment in patients with RPL. We identified that RPL patients have a remarkably decreased number of a particular subset of dNK cells (dNK1), which may contribute to the secretion of growth-promoting factors to promote normal pregnancy 38 . Meanwhile, RPL patients harbor significantly increased numbers of a proinflammatory subset of dNK cells (dNK3) that produce cytokines.…”

Section: Discussionmentioning

confidence: 99%

Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss

et al. 2021

Self Cite

View full text Add to dashboard Cite

Maintaining homeostasis of the decidual immune microenvironment at the maternal–fetal interface is essential for placentation and reproductive success. Although distinct decidual immune cell subpopulations have been identified under normal conditions, systematic understanding of the spectrum and heterogeneity of leukocytes under recurrent miscarriage in human deciduas remains unclear. To address this, we profiled the respective transcriptomes of 18,646 primary human decidual immune cells isolated from patients with recurrent pregnancy loss (RPL) and healthy controls at single-cell resolution. We discovered dramatic differential distributions of immune cell subsets in RPL patients compared with the normal decidual immune microenvironment. Furthermore, we found a subset of decidual natural killer (NK) cells that support embryo growth were diminished in proportion due to abnormal NK cell development in RPL patients. We also elucidated the altered cellular interactions between the decidual immune cell subsets in the microenvironment and those of the immune cells with stromal cells and extravillous trophoblast under disease state. These results provided deeper insights into the RPL decidual immune microenvironment disorder that are potentially applicable to improve the diagnosis and therapeutics of this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Intestinal Lin − NKp46 + NK1.1 + cells consist of Eomes + RORγt-fate map − cNK cells, which express CD27 and lack IL-7Rα, along with a smaller fraction of Eomes − RORγt-fate map + NK cells [ 103 ] that is similar to liver-resident NK cells [ 104 ]. Thus, cNK and trNK cells significantly differ in their requirement of the developmental niche and transcriptional networks [ 105 , 106 ]. The topological organization of trNK cells within the microenvironment in organs such as lung or uterus holds clues about their functions, interacting partners, and cellular signals [ 107 , 108 , 109 , 110 ].…”

Section: Cnk Versus Trnk Cellsmentioning

confidence: 99%

Tissue-Resident NK Cells: Development, Maturation, and Clinical Relevance

Hashemi

Malarkannan

2020

Cancers

View full text Add to dashboard Cite

Natural killer (NK) cells belong to type 1 innate lymphoid cells (ILC1) and are essential in killing infected or transformed cells. NK cells mediate their effector functions using non-clonotypic germ-line-encoded activation receptors. The utilization of non-polymorphic and conserved activating receptors promoted the conceptual dogma that NK cells are homogeneous with limited but focused immune functions. However, emerging studies reveal that NK cells are highly heterogeneous with divergent immune functions. A distinct combination of several activation and inhibitory receptors form a diverse array of NK cell subsets in both humans and mice. Importantly, one of the central factors that determine NK cell heterogeneity and their divergent functions is their tissue residency. Decades of studies provided strong support that NK cells develop in the bone marrow. However, evolving evidence supports the notion that NK cells also develop and differentiate in tissues. Here, we summarize the molecular basis, phenotypic signatures, and functions of tissue-resident NK cells and compare them with conventional NK cells.

show abstract

“…The CD11b-CD27-property of dNKc manifests their immature characteristic and the potential to differentiate (Fu et al, 2011). Specific expression of PBX1 was found in CD27-CD11b-dNK cells, and a recent study demonstrated the association of decreased PBX1 expression or PBX1 G21S mutation with unexplained RSA (Zhou et al, 2020), further suggesting the crucial role of this dNK subset in pregnancy maintenance. Interestingly, a recently identified pregnancy trained dNK (PTdNK) share similar features with dNKc or dNK1 (Gamliel et al, 2018b), and this subset has been speculated to be enriched and boost decidua receptivity in subsequent pregnancy, therefore may be responsible for the "memory" of reproductive outcomes in next pregnancies.…”

Section: Comparison Of the Differential Gene Expression In Dnk Subsetmentioning

confidence: 90%

Single-cell immune landscape of human recurrent spontaneous abortion

Wang

Jia

Fan

et al. 2020

Preprint

View full text Add to dashboard Cite

SUMMARYSuccessful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent spontaneous abortion (RSA). However, an in-depth understanding of the disorders from the aspect of systematic and decidual immune environment in RSA remains largely lacking. In this study, we utilized single-cell RNA-sequencing to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and RSA pregnancies at the early stage of gestation. Integrative analysis identified 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RSA cases was revealed. Specifically, the cytotoxic properties of CD8T effector, NK, and MAIT cells in peripheral blood indicated apparently enhanced immune inflammatory status, and the subpopulation proportions and ligand-receptor interactions of the decidual leukocyte subsets demonstrated preferential immune activation in RSA patients. The molecular features, spatial distribution and the developmental trajectories of five decidual NK (dNK) subsets were illustrated. The proportion of a dNK subset responsible for fetal protection was reduced, while the ratio of another dNK subset with cytotoxic and immune-active signature was significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subpopulation was substantially accumulated in RSA decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy, which provides an in-depth insight into the immune pathogenesis for early pregnancy loss.

show abstract

PBX1 expression in uterine natural killer cells drives fetal growth

Cited by 64 publications

References 43 publications

Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss

Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss

Tissue-Resident NK Cells: Development, Maturation, and Clinical Relevance

Single-cell immune landscape of human recurrent spontaneous abortion

Contact Info

Product

Resources

About