Adipose Network

Adipose Network - Datasets

Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile the activity of gene regulatory elements in diverse cell types and tissues in the human body, we applied single-cell chromatin accessibility assays to 30 adult human tissue types from multiple donors. We integrated these datasets with single-cell chromatin accessibility data from 15 fetal tissue types to reveal the status of open chromatin for approximately 1.2 million candidate cis-regulatory elements (cCREs) in 222 distinct cell types comprised of >1.3 million nuclei. We used these chromatin accessibility maps to delineate cell type-specificity of fetal and adult human cCREs and to systematically interpret the noncoding variants associated with complex human traits and diseases. This rich resource provides a foundation for the analysis of gene regulatory programs in human cell types across tissues, life stages, and organ systems. Overall design: Applying single cell chromatin accessibility assays to diverse human tissue types from four donors.

A single-cell atlas of chromatin accessibility in the human genome

Single-cell RNA sequencing was used to determine the cell type composition of all major human organs and construct a basic scheme for the human cell landscape (HCL).

Construction of A Human Cell Landscape by Single-cell mRNA-seq

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing.

Cross-tissue immune cell analysis reveals tissue-specific features in humans

Fatty tissue can expand in two ways: through increases in the size of individual adipocytes or through increases in the number of adipocytes. The former process promotes metabolic disease, and the latter protects against it. Merrick et al. used single-cell RNA sequencing to define the hierarchy of mesenchymal progenitor cells that give rise to adipose tissue in mice and humans. They found that progenitor cells expressing a protein called DPP4 give rise to two distinct types of preadipocytes in response to different signals. The DPP4 progenitors reside in a fluid-filled network of collagen and elastin fibers surrounding adipose tissue. In principle, therapeutic interventions that increase progenitor cell differentiation into adipocytes could ameliorate metabolic disease.

Identification of a mesenchymal progenitor cell hierarchy in adipose tissue (scRNA-seq)

Peripheral blood and adipose tissue were collected from eight healthy donors and eight multiple sclerosis (MS) patients. Two of the MS patients were untreated and the rest had previously received disease modifying treatments (DMTs). This study compared the transcriptomic program induced by oleic acid to that of the pro-inflammatory arachidonic acid. The role of fatty acids in regulating tissue inflammatory signals was investigated in healthy donors and MS patients by comparing single-cell transcriptomic profiles of blood and adipose tissue samples with in vitro stimulated Treg cells.

Oleic acid restores suppressive defects in tissue-resident FOXP3 Tregs from patients with multiple sclerosis'

We isolated single cells (using either liberase or collagenase A dissociation) from subcutaneous adipose tissue collected from abdominoplasty surgery, and healthy liver tissue adjacent to tumor from liver resection and ran 10X v2 3' scRNA Seq.

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

We have created a compendium of single cell transcriptome data from the model
organism Mus musculus comprising more than 100,000 cells from 20 organs and
tissues. These data represent a new resource for cell biology, revealing gene
expression in poorly characterized cell populations and allowing for direct and
controlled comparison of gene expression in cell types shared between tissues, such
as T-lymphocytes and endothelial cells from distinct anatomical locations. Two
distinct technical approaches were used for most tissues: one approach, microfluidic
droplet-based 3’-end counting, enabled the survey of thousands of cells at relatively
low coverage, while the other, FACS-based full length transcript analysis, enabled
characterization of cell types with high sensitivity and coverage. The cumulative
data provide the foundation for an atlas of transcriptomic cell biology.

Tabula Muris: Transcriptomic characterization of 20 organs and tissues from Mus musculus at single cell resolution

In recent years there has been tremendous progress towards deep molecular characterization of cell types using single cell transcriptome sequencing. Here we report a single cell transcriptomic atlas comprising nearly 500,000 cells from 24 different human tissues and organs. In several instances multiple organs were analyzed from the same donor. Analyzing organs from the same individual controls for genetic background, age, environment, and epigenetic effects, and enables a detailed comparison of cell types that are shared between tissues. This resource provides a rich molecular characterization of more than 400 cell types, their distribution across tissues, and detailed information about tissue specific variation in gene expression. We have used the fact that multiple tissues came from the same donor to study the clonal distribution of T cells between tissues, to understand the tissue specific mutation rate in B cells, and to analyze the cell cycle state and proliferative potential of shared cell types across tissues. Finally, we have also used this data to characterize cell type specific RNA splicing and how such splicing varies across tissues within an individual.

The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans

Rhabdomyosarcoma (RMS) is the most soft tissue sarcoma of childhood and histologically mimics developing skeletal muscle. To better understand RMS, we performed single-cell RNA-seq of one embryonal subtype RMS (ERMS) and one alveolar subtype RMS (ARMS). We expanded our observations by performing single-nucleus RNA-seq of 18 patient tumors (12 ERMS, 6 ARMS). All 18 of these tumors were used to generate orthotopic patient-derived xenografts, and we performed single-cell RNA-seq of all 18 O-PDXs to compare heterogeneity between the original tumor and the patient-derived model. 15 of the O-PDXs underwent lentiviral barcoding, and lineage could be tracked using a separate dial-out PCR step during the single-cell RNA-seq workflow. We performed single-cell RNA-seq of an ex vivo organoid, showing that we can preserve heterogeneity in this model. We expanded our study to the epigenetic level by using single-cell ATAC-sequencing of 7 O-PDXs. Finally, we longitudinally tracked shifts in heterogeneity in an O-PDX model treated with chemotherapy. Overall design: We performed single-cell RNA-seq from 2 patient RMS tumors, 18 O-PDXs, and 1 organoid. Additionally, we performed single-nucleus RNA-seq from 18 patient RMS tumors and single-cell ATAC-seq from 7 O-PDXs. We also provide dialout PCR data from 15 RMS O-PDX that were used for lentiviral barcode experiments to track clonal lineages within O-PDXs.

Project Title	Species	Method	Anatomical Entity	Disease (Donor)	Cell Count Est.
A single-cell atlas of chromatin accessibility in the human genome	Homo sapiens	sci-RNA-seq	18 anatomical entities	normal	500,000
Construction of A Human Cell Landscape by Single-cell mRNA-seq	Homo sapiens	Microwell-Seq	37 anatomical entities	normal 19 diseases	702,968
Cross-tissue immune cell analysis reveals tissue-specific features in humans	Homo sapiens	6 library construction methods	10 anatomical entities	normal	357,211
Identification of a mesenchymal progenitor cell hierarchy in adipose tissue (scRNA-seq)	2 species	10X 3' v2 sequencing	adipose tissue	normal	22,761
Oleic acid restores suppressive defects in tissue-resident FOXP3 Tregs from patients with multiple sclerosis'	Homo sapiens	Smart-seq2	2 anatomical entities	normal multiple sclerosis	11,724
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.	Homo sapiens	10x 3' v2	2 anatomical entities	normal liver cancer	24,250
Tabula Muris: Transcriptomic characterization of 20 organs and tissues from Mus musculus at single cell resolution	Mus musculus	Smart-seq2	18 anatomical entities	normal	100,605
The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans	Homo sapiens	3 library construction methods	24 anatomical entities	normal 10 diseases	481,120
The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma	Homo sapiens	5 library construction methods	12 anatomical entities	2 diseases	764,251