Innate Immune Responses to Acute Viral Infection During Pregnancy DOI Creative Commons
Emily F. Cornish, Iva Filipovic, Fredrika Åsenius

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 30, 2020

Immunological adaptations in pregnancy allow maternal tolerance of the semi-allogeneic fetus but also increase susceptibility to infection. At implantation, endometrial stroma, glands, arteries and immune cells undergo anatomical functional transformation create decidua, specialized secretory endometrium pregnancy. The decidua invading fetal trophoblast constitute a dynamic junction that facilitates complex immunological dialogue between two. decidual peripheral systems together assume pivotal role regulating critical balance defense against Throughout pregnancy, this equilibrium is repeatedly subjected microbial challenge. Acute viral infection associated with wide spectrum adverse consequences for both mother fetus. Vertical transmission from can cause developmental anomalies, growth restriction, preterm birth stillbirth, while predisposed heightened morbidity death. A rapid, effective response invasive pathogens therefore essential order avoid overwhelming consequent compromise. This sentinel mediated by innate system: heritable, highly evolutionarily conserved system comprising physical barriers, antimicrobial peptides (AMP) variety cells-principally neutrophils, macrophages, dendritic cells, natural killer cells-which express pattern-receptors detect invariant molecular signatures unique pathogenic micro-organisms. Recognition these during acute triggers signaling cascades enhance properties such as phagocytosis, secretion pro-inflammatory cytokines activation complement system. As well coordinating initial response, macrophages present antigens lymphocytes, initiating influencing development specific, long-lasting adaptive immunity. Despite extensive progress unraveling pregnant women remain particularly susceptible certain infections continue experience mortality rates equivalent those observed pandemics several decades ago. Here, we focus specifically on pregnancy-induced vulnerabilities immunity contribute disproportionately high following infections: Lassa fever, Ebola virus disease (EVD), dengue hepatitis E, influenza, novel coronavirus infections.

Language: Английский

CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand–receptor complexes DOI
Mirjana Efremova,

Miquel Vento-Tormo,

Sarah A. Teichmann

et al.

Nature Protocols, Journal Year: 2020, Volume and Issue: 15(4), P. 1484 - 1506

Published: Feb. 26, 2020

Language: Английский

Citations

2567
Deciphering cell–cell interactions and communication from gene expression DOI Open Access
Erick Armingol, Adam Officer, Olivier Harismendy

et al.

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(2), P. 71 - 88

Published: Nov. 9, 2020

Language: Английский

Citations

921
A human cell atlas of fetal gene expression DOI
Junyue Cao,

Diana R. O’Day,

Hannah A. Pliner

et al.

Science, Journal Year: 2020, Volume and Issue: 370(6518)

Published: Nov. 12, 2020

The genomics of human development Understanding the trajectory a developing requires an understanding how genes are regulated and expressed. Two papers now present pooled approach using three levels combinatorial indexing to examine single-cell gene expression chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements RNA broadly distributed cell types provide insights into organ specificity. Domcke examined accessibility cells these identify regulatory elements that regulate expression. Together, analyses generate comprehensive atlases early development. Science , this issue p. eaba7721 eaba7612

Language: Английский

Citations

620
Human placenta and trophoblast development: key molecular mechanisms and model systems DOI Creative Commons
Martin Knöfler, Sandra Haider, Leila Saleh

et al.

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(18), P. 3479 - 3496

Published: May 3, 2019

Abnormal placentation is considered as an underlying cause of various pregnancy complications such miscarriage, preeclampsia and intrauterine growth restriction, the latter increasing risk for development severe disorders in later life cardiovascular disease type 2 diabetes. Despite their importance, molecular mechanisms governing human placental formation trophoblast cell lineage specification differentiation have been poorly unravelled, mostly due to lack appropriate cellular model systems. However, over past few years major progress has made by establishing self-renewing stem cells 3-dimensional organoids from blastocysts early tissues opening path detailed investigations. Herein, we summarize present knowledge about development, its cells, progenitors differentiated types epithelium villous core. Anatomy placenta, current systems, critical key regulatory factors signalling cascades will be elucidated. In this context, discuss role developmental pathways Wingless Notch, controlling stemness/differentiation invasive progenitors, respectively.

Language: Английский

Citations

610
Development of the human placenta DOI Creative Commons
Margherita Y. Turco, Ashley Moffett

Development, Journal Year: 2019, Volume and Issue: 146(22)

Published: Nov. 15, 2019

ABSTRACT The placenta is essential for normal in utero development mammals. In humans, defective placental formation underpins common pregnancy disorders such as pre-eclampsia and fetal growth restriction. great variation types across mammals means that animal models have been of limited use understanding human development. However, new tools studying development, including 3D organoids, stem cell culture systems single RNA sequencing, brought insights into this field. Here, we review the morphological, molecular functional aspects formation, with a focus on defining – trophoblast.

Language: Английский

Citations

538
Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle DOI
Wanxin Wang, Felipe Vilella, Pilar Alamá

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(10), P. 1644 - 1653

Published: Sept. 14, 2020

Language: Английский

Citations

425
A human cell atlas of fetal chromatin accessibility DOI
Silvia Domcke, Andrew J. Hill, Riza M. Daza

et al.

Science, Journal Year: 2020, Volume and Issue: 370(6518)

Published: Nov. 13, 2020

The genomics of human development Understanding the trajectory a developing requires an understanding how genes are regulated and expressed. Two papers now present pooled approach using three levels combinatorial indexing to examine single-cell gene expression chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements RNA broadly distributed cell types provide insights into organ specificity. Domcke examined accessibility cells these identify regulatory elements that regulate expression. Together, analyses generate comprehensive atlases early development. Science , this issue p. eaba7721 eaba7612

Language: Английский

Citations

360
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics DOI Creative Commons
Christoph Muus, Malte D. Luecken,

Gökcen Eraslan

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(3), P. 546 - 559

Published: March 1, 2021

Language: Английский

Citations

314
Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells DOI Creative Commons

Christoph Muus,

Malte D. Luecken,

Gökcen Eraslan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: April 20, 2020

ABSTRACT The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) associated proteases, transmembrane protease serine (TMPRSS2) Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess cell type-specific RNA expression ACE2 , TMPRSS2 CTSL through integrated analysis 107 single-cell single-nucleus RNA-Seq studies, including 22 lung airways datasets (16 unpublished), 85 from other diverse organs. Joint accessory proteases identifies specific subsets respiratory epithelial cells putative targets infection in nasal passages, airways, alveoli. Cells co-express are also organs, some which have been with transmission or pathology, gut enterocytes, corneal cells, cardiomyocytes, heart pericytes, olfactory sustentacular renal cells. Performing first meta-analyses scRNA-seq analyzed 1,176,683 282 nasal, airway, parenchyma samples 164 donors spanning fetal, childhood, adult, elderly age groups, associate increased levels types increasing age, male gender, smoking, all epidemiologically linked to susceptibility outcomes. Notably, there was a particularly low few young pediatric analysis. Further reveals gene program shared + tissues, genes may subtend key immune functions, epithelial-macrophage cross-talk. Amongst these IL6, its receptor co-receptor, IL1R TNF response pathways, complement genes. type specificity smoking effects conserved mice. Our analyses suggest differences SARS-CoV-2 entry be responsible aspects epidemiology clinical course, point pathways involved disease pathogenesis.

Language: Английский

Citations

263
Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface DOI Creative Commons
Alice Lu-Culligan, Arun R. Chavan, Pavithra Vijayakumar

et al.

Med, Journal Year: 2021, Volume and Issue: 2(5), P. 591 - 610.e10

Published: April 30, 2021

BackgroundPregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this morbidity and its potential effect on developing fetus is not well understood.MethodsWe assessed placental histology, ACE2 expression, viral immune dynamics term placenta in pregnant with without respiratory acute syndrome 2 (SARS-CoV-2) infection.FindingsThe majority (13 of 15) placentas analyzed had no detectable RNA. was detected by immunohistochemistry syncytiotrophoblast cells normal during early pregnancy rarely seen healthy full term, suggesting that low expression may protect infection. Using immortalized cell lines primary isolated cells, we found cytotrophoblasts, trophoblast stem precursors to syncytiotrophoblasts, rather than syncytiotrophoblasts or Hofbauer most vulnerable SARS-CoV-2 infection vitro. To better understand mechanisms shielding vivo, performed bulk single-cell transcriptomics analyses maternal-fetal interface SARS-CoV-2-infected exhibited robust responses, including activation natural killer (NK) T interferon-related genes, as markers associated complications such preeclampsia.ConclusionsSARS-CoV-2 late even absence local invasion.FundingNIH (T32GM007205, F30HD093350, K23MH118999, R01AI157488, U01DA040588) Fast Grant funding support Emergent Ventures Mercatus Center.

Language: Английский

Citations

178