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Article ; Online: Lung Cell Atlases in Health and Disease.

Adams, Taylor S / Marlier, Arnaud / Kaminski, Naftali

2022 Volume 85, Page(s) 47–69

Abstract: The human lung cellular portfolio, traditionally characterized by cellular morphology and individual markers, is highly diverse, with over 40 cell types and a complex branching structure highly adapted for agile airflow and gas exchange. While constant ... ...

Abstract	The human lung cellular portfolio, traditionally characterized by cellular morphology and individual markers, is highly diverse, with over 40 cell types and a complex branching structure highly adapted for agile airflow and gas exchange. While constant during adulthood, lung cellular content changes in response to exposure, injury, and infection. Some changes are temporary, but others are persistent, leading to structural changes and progressive lung disease. The recent advance of single-cell profiling technologies allows an unprecedented level of detail and scale to cellular measurements, leading to the rise of comprehensive cell atlas styles of reporting. In this review, we chronical the rise of cell atlases and explore their contributions to human lung biology in health and disease.
MeSH term(s)	Humans ; Adult ; Lung/physiology
Language	English
Publishing date	2022-11-09
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207933-1
ISSN	1545-1585 ; 0066-4278
ISSN (online)	1545-1585
ISSN	0066-4278
DOI	10.1146/annurev-physiol-032922-082826
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Article: Dedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease.

Chandran, Rachana R / Adams, Taylor S / Kabir, Inamul / Gallardo-Vara, Eunate / Kaminski, Naftali / Gomperts, Brigitte N / Greif, Daniel M

Frontiers in cell and developmental biology

2024 Volume 12, Page(s) 1335061

Abstract: Alveolarization ensures sufficient lung surface area for gas exchange, and during bulk alveolarization in mice (postnatal day [P] 4.5-14.5), alpha-smooth muscle actin (SMA) ...

Abstract	Alveolarization ensures sufficient lung surface area for gas exchange, and during bulk alveolarization in mice (postnatal day [P] 4.5-14.5), alpha-smooth muscle actin (SMA)
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2024.1335061
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Article ; Online: Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea.

Cortese, Rene / Adams, Taylor S / Cataldo, Kylie H / Hummel, Justin / Kaminski, Naftali / Kheirandish-Gozal, Leila / Gozal, David

The European respiratory journal

2023 Volume 61, Issue 2

Abstract: Background: Obstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on ... ...

Abstract	Background: Obstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined. Methods: We applied single-cell transcriptomics analysis (scRNA-seq) to identify OSA-induced changes in transcriptional landscape in peripheral blood mononuclear cell (PBMC) composition, which uncovered severity-dependent differences in several cell lineages. Furthermore, a machine-learning approach was used to combine scRNAs-seq cell-specific markers with those differentially expressed in OSA. Results: scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs. We identified a molecular signature consisting of 32 genes, which distinguished OSA patients from various controls with high precision (area under the curve 0.96) and accuracy (93% positive predictive value and 95% negative predictive value) in an independent PBMC bulk RNA expression dataset. Conclusion: OSA deregulates systemic immune function and displays a molecular signature that can be assessed in standard cellular RNA without the need for pre-analytical cell separation, thereby making the assay amenable to application in a molecular diagnostic setting.
MeSH term(s)	Adult ; Humans ; Child ; Leukocytes, Mononuclear ; Single-Cell Gene Expression Analysis ; Sleep Apnea, Obstructive ; Inflammation
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.01465-2022
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Article: Dendritic Cell - Fibroblast Crosstalk via TLR9 and AHR Signaling Drives Lung Fibrogenesis.

Carter, Hannah / Costa, Rita Medina / Adams, Taylor S / Gilchrist, Talon / Emch, Claire E / Bame, Monica / Oldham, Justin M / Linderholm, Angela L / Noth, Imre / Kaminski, Naftali / Moore, Bethany B / Gurczynski, Stephen J

bioRxiv : the preprint server for biology

2024

Abstract: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring and loss of lung function. With limited treatment options, patients succumb to the disease within 2-5 years. The molecular pathogenesis of IPF regarding the immunologic changes ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring and loss of lung function. With limited treatment options, patients succumb to the disease within 2-5 years. The molecular pathogenesis of IPF regarding the immunologic changes that occur is poorly understood. We characterize a role for non-canonical aryl-hydrocarbon receptor signaling (ncAHR) in dendritic cells (DCs) that leads to production of IL-6 and IL-17, promoting fibrosis. TLR9 signaling in myofibroblasts is shown to regulate production of TDO2 which converts tryptophan into the endogenous AHR ligand kynurenine. Mice with augmented ncAHR signaling were created by crossing floxed AHR exon-2 deletion mice (AHR
Language	English
Publishing date	2024-03-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.15.584457
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Article ; Online: Rational engineering of lung alveolar epithelium.

Leiby, Katherine L / Yuan, Yifan / Ng, Ronald / Raredon, Micha Sam Brickman / Adams, Taylor S / Baevova, Pavlina / Greaney, Allison M / Hirschi, Karen K / Campbell, Stuart G / Kaminski, Naftali / Herzog, Erica L / Niklason, Laura E

NPJ Regenerative medicine

2023 Volume 8, Issue 1, Page(s) 22

Abstract: Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, ... ...

Abstract	Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds in order to guide AEC2 behavior for epithelial regeneration. First, endothelial cells coordinate with fibroblasts, in the presence of soluble growth and maturation factors, to promote alveolar scaffold population with surfactant-secreting AEC2s. Subsequent withdrawal of Wnt and FGF agonism synergizes with tidal-magnitude mechanical strain to induce the differentiation of AEC2s to squamous type 1 AECs (AEC1s) in cultured alveoli, in situ. These results outline a rational strategy to engineer an epithelium of AEC2s and AEC1s contained within epithelial-mesenchymal-endothelial alveolar-like units, and highlight the critical interplay amongst cellular, biochemical, and mechanical niche cues within the reconstituting alveolus.
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article
ISSN	2057-3995
ISSN (online)	2057-3995
DOI	10.1038/s41536-023-00295-2
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Article ; Online: Emergence of division of labor in tissues through cell interactions and spatial cues.

Adler, Miri / Moriel, Noa / Goeva, Aleksandrina / Avraham-Davidi, Inbal / Mages, Simon / Adams, Taylor S / Kaminski, Naftali / Macosko, Evan Z / Regev, Aviv / Medzhitov, Ruslan / Nitzan, Mor

Cell reports

2023 Volume 42, Issue 5, Page(s) 112412

Abstract: Most cell types in multicellular organisms can perform multiple functions. However, not all functions can be optimally performed simultaneously by the same cells. Functions incompatible at the level of individual cells can be performed at the cell ... ...

Abstract	Most cell types in multicellular organisms can perform multiple functions. However, not all functions can be optimally performed simultaneously by the same cells. Functions incompatible at the level of individual cells can be performed at the cell population level, where cells divide labor and specialize in different functions. Division of labor can arise due to instruction by tissue environment or through self-organization. Here, we develop a computational framework to investigate the contribution of these mechanisms to division of labor within a cell-type population. By optimizing collective cellular task performance under trade-offs, we find that distinguishable expression patterns can emerge from cell-cell interactions versus instructive signals. We propose a method to construct ligand-receptor networks between specialist cells and use it to infer division-of-labor mechanisms from single-cell RNA sequencing (RNA-seq) and spatial transcriptomics data of stromal, epithelial, and immune cells. Our framework can be used to characterize the complexity of cell interactions within tissues.
MeSH term(s)	Cues ; Cell Communication ; Gene Expression Profiling
Language	English
Publishing date	2023-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112412
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Article ; Online: Correction: iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects.

Liu, Yunqing / Zhao, Jiayi / Adams, Taylor S / Wang, Ningya / Schupp, Jonas C / Wu, Weimiao / McDonough, John E / Chupp, Geoffrey L / Kaminski, Naftali / Wang, Zuoheng / Yan, Xiting

BMC bioinformatics

2023 Volume 24, Issue 1, Page(s) 394

Language	English
Publishing date	2023-10-19
Publishing country	England
Document type	Published Erratum
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-023-05523-6
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Article ; Online: iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects.

Liu, Yunqing / Zhao, Jiayi / Adams, Taylor S / Wang, Ningya / Schupp, Jonas C / Wu, Weimiao / McDonough, John E / Chupp, Geoffrey L / Kaminski, Naftali / Wang, Zuoheng / Yan, Xiting

BMC bioinformatics

2023 Volume 24, Issue 1, Page(s) 318

Abstract: Background: Single-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect ... ...

Abstract	Background: Single-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect contributes to the major source of variation in scRNA-seq data with multiple subjects, which severely confounds cell type specific differential expression (DE) analysis. Moreover, dropout events are prevalent in scRNA-seq data, leading to excessive number of zeroes in the data, which further aggravates the challenge in DE analysis. Results: We developed iDESC to detect cell type specific DE genes between two groups of subjects in scRNA-seq data. iDESC uses a zero-inflated negative binomial mixed model to consider both subject effect and dropouts. The prevalence of dropout events (dropout rate) was demonstrated to be dependent on gene expression level, which is modeled by pooling information across genes. Subject effect is modeled as a random effect in the log-mean of the negative binomial component. We evaluated and compared the performance of iDESC with eleven existing DE analysis methods. Using simulated data, we demonstrated that iDESC had well-controlled type I error and higher power compared to the existing methods. Applications of those methods with well-controlled type I error to three real scRNA-seq datasets from the same tissue and disease showed that the results of iDESC achieved the best consistency between datasets and the best disease relevance. Conclusions: iDESC was able to achieve more accurate and robust DE analysis results by separating subject effect from disease effect with consideration of dropouts to identify DE genes, suggesting the importance of considering subject effect and dropouts in the DE analysis of scRNA-seq data with multiple subjects.
MeSH term(s)	Humans ; Models, Statistical ; Transcriptome ; Sequence Analysis, RNA
Language	English
Publishing date	2023-08-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-023-05432-8
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Article ; Online: Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs

Obacz, Joanna / Valer, Jose Antonio / Nibhani, Reshma / Adams, Taylor S / Schupp, Jonas C / Veale, Niki / Lewis-Wade, Amanah / Flint, Jasper / Hogan, John / Aresu, Giuseppe / Coonar, Aman S / Peryt, Adam / Biffi, Giulia / Kaminski, Naftali / Francies, Hayley / Rassl, Doris M / Garnett, Mathew J / Rintoul, Robert C / Marciniak, Stefan J

The European respiratory journal

2024 Volume 63, Issue 1

Abstract: The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal ... ...

Abstract	The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here, we present the first comprehensive single-cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple
MeSH term(s)	Humans ; Pleura/pathology ; Mesothelioma/genetics ; Mesothelioma/pathology ; Mesothelioma, Malignant/pathology ; Pleural Neoplasms/genetics ; Pleural Neoplasms/pathology ; Gene Expression Profiling
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.00143-2023
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Article: A Multi-omic Analysis of the Human Lung Reveals Distinct Cell Specific Aging and Senescence Molecular Programs.

De Man, Ruben / McDonough, John E / Adams, Taylor S / Manning, Edward P / Myers, Greg / Vos, Robin / Ceulemans, Laurens / Dupont, Lieven / Vanaudenaerde, Bart M / Wuyts, Wim A / Rosas, Ivan O / Hagood, James S / Ambalavanan, Namasivayam / Niklason, Laura / Hansen, Kirk C / Yan, Xiting / Kaminski, Naftali

bioRxiv : the preprint server for biology

2023

Abstract: Age is a major risk factor for lung disease. To understand the mechanisms underlying this association, we characterized the changing cellular, genomic, transcriptional, and epigenetic landscape of lung aging using bulk and single-cell RNAseq (scRNAseq) ... ...

Abstract	Age is a major risk factor for lung disease. To understand the mechanisms underlying this association, we characterized the changing cellular, genomic, transcriptional, and epigenetic landscape of lung aging using bulk and single-cell RNAseq (scRNAseq) data. Our analysis revealed age-associated gene networks that reflected hallmarks of aging, including mitochondrial dysfunction, inflammation, and cellular senescence. Cell type deconvolution revealed age-associated changes in the cellular composition of the lung: decreased alveolar epithelial cells and increased fibroblasts and endothelial cells. In the alveolar microenvironment, aging is characterized by decreased AT2B cells and reduced surfactant production, a finding that was validated by scRNAseq and IHC. We showed that a previously reported senescence signature, SenMayo, captures cells expressing canonical senescence markers. SenMayo signature also identified cell-type specific senescence-associated co-expression modules that have distinct molecular functions, including ECM regulation, cell signaling, and damage response pathways. Analysis of somatic mutations showed that burden was highest in lymphocytes and endothelial cells and was associated with high expression of senescence signature. Finally, aging and senescence gene expression modules were associated with differentially methylated regions, with inflammatory markers such as
Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.19.536722
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