Single-Cell Chromatin Analysis of Mammary Gland Development Reveals Cell-State Transcriptional Regulators and Lineage Relationships

Chung, Chi‐Yeh; Ma, Zhibo; Dravis, Christopher; Preißl, Sebastian; Poirion, Olivier; Luna, Gidsela; Hou, Xiaomeng; Giraddi, Rajshekhar R.; Ren, Bing; Wahl, Geoffrey M.

doi:10.1016/j.celrep.2019.08.089

Cited by 83 publications

(82 citation statements)

References 70 publications

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“…An advantage of snATAC-seq is the ability to measure covariance between accessible chromatin sites to predict cis-regulatory interactions 14 . This approach can link putative regulatory regions with their target genes and has been applied to human pancreatic islets 73 , acute leukemia 74 , and multiple mouse tissues, including: hippocampus 75 , mammary gland 76 , T-cells 77 , and kidney among others 8,9 . In particular, genome wide association study (GWAS) risk loci can be linked to their target genes, which would complement the progress made using chromosome conformation capture (Hi-C) 33 .…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Wilson

Waikar

et al. 2020

Preprint

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The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA (snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely-associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NFκB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. These datasets can be visualized at this resource: http://humphreyslab.com/SingleCell/. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.

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Section: Discussionmentioning

confidence: 99%

Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Wilson

Waikar

et al. 2020

Preprint

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“…The epigenetic alterations modulate the chromatin accessibility and regulate the gene expression during the differentiation of stem into differentiated cells [49], being essential for the transcriptional plasticity and tissue-specific cell differentiation throughout the mammary gland development [50,51]. The mammary gland shows several changes in its architecture throughout the lifetime, mainly in response to hormones.…”

Section: Epigenetic Of Mammary Gland Differentiation and Developmentmentioning

confidence: 99%

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

Faldoni

Rainho

Rogatto

2020

Cells

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Evidence has emerged implicating epigenetic alterations in inflammatory breast cancer (IBC) origin and progression. IBC is a rare and rapidly progressing disease, considered the most aggressive type of breast cancer (BC). At clinical presentation, IBC is characterized by diffuse erythema, skin ridging, dermal lymphatic invasion, and peau d’orange aspect. The widespread distribution of the tumor as emboli throughout the breast and intra- and intertumor heterogeneity is associated with its poor prognosis. In this review, we highlighted studies documenting the essential roles of epigenetic mechanisms in remodeling chromatin and modulating gene expression during mammary gland differentiation and the development of IBC. Compiling evidence has emerged implicating epigenetic changes as a common denominator linking the main risk factors (socioeconomic status, environmental exposure to endocrine disruptors, racial disparities, and obesity) with IBC development. DNA methylation changes and their impact on the diagnosis, prognosis, and treatment of IBC are also described. Recent studies are focusing on the use of histone deacetylase inhibitors as promising epigenetic drugs for treating IBC. All efforts must be undertaken to unravel the epigenetic marks that drive this disease and how this knowledge could impact strategies to reduce the risk of IBC development and progression.

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“…The ''FindClusters'' function was used to cluster cells with a resolution of 0.80, and cells were visualized using the "RunTSNE" function within Seurat in R. In addition, differential expression analyses for each cluster were performed with a likelihood-ratio test for single-cell gene expression by using the default parameters via the "FindAllMarkers" function again in Seurat. Cluster cell identity was assigned by manual annotation while using known marker genes from already published papers [10][11][12][13][14].…”

Section: Cell Type Clusters and Marker Genes Identi Cationmentioning

confidence: 99%

“…Single-cell RNA Sequencing (scRNA-Seq) allows cellular heterogeneity and functional pro les at the single-cell level to be examined [9]. In recent years, several studies have gradually improved this powerful technique to explore the cell type/subtype pro les, function and fate state of individual cells, communication paths, and developmental trajectories in different cell subtypes in the MG of both mice [10][11][12] and humans [13,14]. This approach revealed a series of novel cell subsets, their marker genes, and interactions in the MG.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA-Aequencing Reveals Novel Myofibroblasts with Epithelial Cell-Like Features in the Mammary Gland of Dairy Cattle

Gu¹,

Wu²,

Zhu³

et al. 2020

Preprint

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Background: Cow’s milk is a highly-nutritious dairy product that is widely consumed worldwide. It is secreted by the developed mammary gland (MG) of dairy cattle. However, a comprehensive understanding of cell-type diversity and cell function within bovine MG is lacking. In the current study, we used single-cell RNA sequencing to investigate the transcriptome of 24,472 high-quality MG cells isolated from newborn and adult cows. Results: Unbiased clustering analysis revealed the existence of 24 cell types, which could be divided into four categories: 9 immune, 3 epithelial, 9 fibroblast, and 3 endothelial cell types. Other cell subtypes were further identified based on re-clustering and pseudotemporal reconstruction of epithelial cells that included 3 mature luminal epithelial, 1 intermediate, and 2 progenitor cell subtypes. The individual top marker genes of these 3 mature luminal epithelial cell subtypes (L0, L1, and L5) were APOA1, STC2, and PTX3, which were further validated using immunofluorescence. Based on functional analysis, the L0, L1, and L5 cell subtypes were all involved in the upregulation of lipid metabolism, protein and hormone metabolism, and the immune response, respectively. Furthermore, we discovered a novel myofibroblast that expresses COL1A1 and CSN3, has visible epithelial-like characteristics, and shows the potential to differentiate into luminal epithelial cells, especially immune-sensing luminal cells (L5). Conclusions: We constructed the first single-cell atlas of the dairy cow MG, and our new findings of epithelial-like myofibroblast cells and their differentiation trajectories into luminal cells may provide novel insights into the development and lactogenesis in dairy cattle MGs.

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Single-Cell Chromatin Analysis of Mammary Gland Development Reveals Cell-State Transcriptional Regulators and Lineage Relationships

Cited by 83 publications

References 70 publications

Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

Single-cell RNA-Aequencing Reveals Novel Myofibroblasts with Epithelial Cell-Like Features in the Mammary Gland of Dairy Cattle

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