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

Nature Protocols, Год журнала: 2020, Номер 15(4), С. 1484 - 1506

Опубликована: Фев. 26, 2020

Язык: Английский

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Deciphering cell–cell interactions and communication from gene expression

Nature Reviews Genetics, Год журнала: 2020, Номер 22(2), С. 71 - 88

Опубликована: Ноя. 9, 2020

Язык: Английский

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A human cell atlas of fetal gene expression

Science, Год журнала: 2020, Номер 370(6518)

Опубликована: Ноя. 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

Язык: Английский

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Human placenta and trophoblast development: key molecular mechanisms and model systems

Cellular and Molecular Life Sciences, Год журнала: 2019, Номер 76(18), С. 3479 - 3496

Опубликована: Май 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.

Язык: Английский

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Development of the human placenta

Development, Год журнала: 2019, Номер 146(22)

Опубликована: Ноя. 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.

Язык: Английский

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Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle

Nature Medicine, Год журнала: 2020, Номер 26(10), С. 1644 - 1653

Опубликована: Сен. 14, 2020

Язык: Английский

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A human cell atlas of fetal chromatin accessibility

Science, Год журнала: 2020, Номер 370(6518)

Опубликована: Ноя. 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

Язык: Английский

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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Nature Medicine, Год журнала: 2021, Номер 27(3), С. 546 - 559

Опубликована: Март 1, 2021

Язык: Английский

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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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2020, Номер unknown

Опубликована: Апрель 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.

Язык: Английский

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Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface

Med, Год журнала: 2021, Номер 2(5), С. 591 - 610.e10

Опубликована: Апрель 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.

Язык: Английский

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