scholarly journals A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics

2021 ◽  
Author(s):  
Joseph Burclaff ◽  
R. Jarrett Bliton ◽  
Keith A Breau ◽  
Meryem T Ok ◽  
Ismael Gomez-Martinez ◽  
...  
Keyword(s):  
Small Intestine ◽  
Single Cell ◽  
Drug Targets ◽  
Healthy Adult ◽  
Cellular Level ◽  
Cell Junction ◽  
Marker Genes ◽  
Human Small Intestine ◽  
Adult Human ◽  
Human Intestinal Epithelium

Background and Aims: Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies in healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics from 3 humans covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon. Methods: 12,590 single epithelial cells from three independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and capacity for response to extrinsic signals along the gut axis across different humans. Results: Cells were assigned to 25 epithelial lineage clusters. Human intestinal stem cells (ISCs) are not specifically marked by many murine ISC markers. Lysozyme expression is not unique to Paneth cells (PCs), and PCs lack expression of expected niche-factors. BEST4 cells express NPY and show functional and maturational differences between SI and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell-junction, and nutrient absorption genes show unappreciated regional expression differences across lineages. Differential expression of receptors and drug targets across lineages reveals biological variation and potential for variegated responses. Conclusions: Our study identifies novel lineage marker genes; covers regional differences; shows important differences between mouse and human gut epithelium; and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves data gaps in anatomical regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.

scholarly journals Molecular characteristics and spatial distribution of adult human corneal cell subtypes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ann J. Ligocki ◽  
Wen Fury ◽  
Christian Gutierrez ◽  
Christina Adler ◽  
Tao Yang ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Cross Sections ◽  
Cell Types ◽  
Marker Genes ◽  
Molecular Characteristics ◽  
Transcriptional Level ◽  
Human Cornea ◽  
Adult Human ◽  
And Migration

AbstractBulk RNA sequencing of a tissue captures the gene expression profile from all cell types combined. Single-cell RNA sequencing identifies discrete cell-signatures based on transcriptomic identities. Six adult human corneas were processed for single-cell RNAseq and 16 cell clusters were bioinformatically identified. Based on their transcriptomic signatures and RNAscope results using representative cluster marker genes on human cornea cross-sections, these clusters were confirmed to be stromal keratocytes, endothelium, several subtypes of corneal epithelium, conjunctival epithelium, and supportive cells in the limbal stem cell niche. The complexity of the epithelial cell layer was captured by eight distinct corneal clusters and three conjunctival clusters. These were further characterized by enriched biological pathways and molecular characteristics which revealed novel groupings related to development, function, and location within the epithelial layer. Moreover, epithelial subtypes were found to reflect their initial generation in the limbal region, differentiation, and migration through to mature epithelial cells. The single-cell map of the human cornea deepens the knowledge of the cellular subsets of the cornea on a whole genome transcriptional level. This information can be applied to better understand normal corneal biology, serve as a reference to understand corneal disease pathology, and provide potential insights into therapeutic approaches.

scholarly journals Detection and Characterization of Hemopoietic Stem Cells in the Adult Human Small Intestine

2006 ◽  
Vol 176 (9) ◽  
pp. 5199-5204 ◽  
Author(s):  
Lydia Lynch ◽  
Diarmuid O’Donoghue ◽  
Jonathan Dean ◽  
Jacintha O’Sullivan ◽  
Cliona O’Farrelly ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Intestine ◽  
Hemopoietic Stem Cells ◽  
Human Small Intestine ◽  
Adult Human

scholarly journals Single cell transcriptome atlas of immune cells in human small intestine and in celiac disease

2019 ◽  
Author(s):  
Nader Atlasy ◽  
Anna Bujko ◽  
Peter B Brazda ◽  
Eva Janssen-Megens ◽  
Espen S. Bækkevold ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
Celiac Disease ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Current Knowledge ◽  
Villous Atrophy ◽  
Cellular Heterogeneity ◽  
Human Small Intestine

Celiac disease (CeD) is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine1,2. The CeD lesion is characterized by crypt hyperplasia, villous atrophy and chronic inflammation with accumulation of leukocytes both in the lamina propria (LP) and in the epithelium3, which eventually leads to destruction of the intestinal epithelium1 and subsequent digestive complications and higher risk of non-hodgkin lymphoma4. A lifetime gluten-free diet is currently the only available treatment5. Gluten-specific LP CD4 T cells and cytotoxic intraepithelial CD8+ T cells are thought to be central in disease pathology1,6-8, however, CeD is a complex immune-mediated disorder and to date the findings are mostly based on analysis of heterogeneous cell populations and on animal models. Here, we comprehensively explore the cellular heterogeneity of CD45+ immune cells in human small intestine using index-sorting single-cell RNA-sequencing9,10. We find that myeloid and mast cell transcriptomes are reshaped in CeD. We observe extensive changes in the proportion and transcriptomes of CD4+ and CD8+ T cells and define a CD3zeta expressing NK-T-like cell population present in the control LP and epithelial layers that is absent and replaced in CeD. Our findings show that the immune landscape is dramatically changed in active CeD which provide new insights and considerably extend the current knowledge of CeD immunopathology.

scholarly journals Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs

2020 ◽  
Author(s):  
Shuai He ◽  
Lin-He Wang ◽  
Yang Liu ◽  
Yi-Qi Li ◽  
Hai-Tian Chen ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Cell ◽  
Regulatory Networks ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Cell Receptor ◽  
Marker Genes ◽  
Human Organs ◽  
Adult Human ◽  
Receptor Repertoire

ABSTRACTBackgroundAs core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing.ResultsWe perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH+ fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues.ConclusionsThe adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.

scholarly journals Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuai He ◽  
Lin-He Wang ◽  
Yang Liu ◽  
Yi-Qi Li ◽  
Hai-Tian Chen ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Cell ◽  
Regulatory Networks ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Cell Receptor ◽  
Marker Genes ◽  
Human Organs ◽  
Adult Human ◽  
Receptor Repertoire

Abstract Background As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. Results We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH+ fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. Conclusions The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.

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