scholarly journals A Single-Cell Transcriptome Atlas of the Human Pancreas

Cell Systems ◽  
2016 ◽  
Vol 3 (4) ◽  
pp. 385-394.e3 ◽  
Author(s):  
Mauro J. Muraro ◽  
Gitanjali Dharmadhikari ◽  
Dominic Grün ◽  
Nathalie Groen ◽  
Tim Dielen ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Pancreas ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

scholarly journals A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion

2021 ◽  
Author(s):  
Carla A. Gonçalves ◽  
Michael Larsen ◽  
Sascha Jung ◽  
Johannes Stratmann ◽  
Akiko Nakamura ◽  
...  
Keyword(s):  
Single Cell ◽  
R Package ◽  
Fetal Tissue ◽  
Defined Medium ◽  
Three Dimensions ◽  
Practical Reasons ◽  
Human Pancreas ◽  
Fetal Pancreas ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Human organogenesis remains relatively unexplored for ethical and practical reasons. Here we report the establishment of a single cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell-cell interactions we developed InterCom, an R-Package for identifying receptors-ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2D and those expanded in 3D to fetal tissue reveals that progenitors expanded in 3D are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion.

scholarly journals A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion

2021 ◽  
Author(s):  
Carla A. Gonçalves ◽  
Michael Larsen ◽  
Sascha Jung ◽  
Johannes Stratmann ◽  
Akiko Nakamura ◽  
...  
Keyword(s):  
Single Cell ◽  
R Package ◽  
Fetal Tissue ◽  
Defined Medium ◽  
Three Dimensions ◽  
Practical Reasons ◽  
Human Pancreas ◽  
Fetal Pancreas ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Human organogenesis remains relatively unexplored for ethical and practical reasons. Here we report the establishment of a single cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell-cell interactions we developed InterCom, an R-Package for identifying receptors-ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2D and those expanded in 3D to fetal tissue reveals that progenitors expanded in 3D are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion.

scholarly journals Cell type purification by single-cell transcriptome-trained sorting

2018 ◽  
Author(s):  
Chloé S Baron ◽  
Aditya Barve ◽  
Mauro J Muraro ◽  
Gitanjali Dharmadhikari ◽  
Reinier van der Linden ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Sorting ◽  
Cell Types ◽  
Computational Method ◽  
Human Pancreas ◽  
Cell Type ◽  
Specific Antibodies ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Index Sorting

Traditional cell type enrichment using fluorescence activated cell sorting (FACS) relies on methods that specifically label the cell type of interest. Here we propose GateID, a computational method that combines single-cell transcriptomics for unbiased cell type identification with FACS index sorting to purify cell types of choice. We validate GateID by purifying various cell types from the zebrafish kidney marrow and the human pancreas without resorting to specific antibodies or transgenes.

scholarly journals Single cell transcriptome analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns

2017 ◽  
Author(s):  
Martin Enge ◽  
H. Efsun Arda ◽  
Marco Mignardi ◽  
John Beausang ◽  
Rita Bottino ◽  
...  
Keyword(s):  
Single Cell ◽  
Transcriptome Analysis ◽  
Human Tissue ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Tumor Cell Line ◽  
Human Pancreas ◽  
Human Brain Tissue ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractAs organisms age, cells accumulate genetic and epigenetic changes that eventually lead to impaired organ function or catastrophic transformation such as cancer. Since aging appears to be a stochastic process of increasing disorder1 cells in an organ will be individually affected in different ways - thus rendering bulk analyses of postmitotic adult tissues difficult to characterize. Here we directly measure the effects of aging in primary human tissue by performing single-cell transcriptome analysis of 2544 human pancreas cells from eight donors spanning six decades of life. We find that islet cells from older donors have increased levels of molecular disorder as measured both by noise in the transcriptome and by the number of cells which display inappropriate hormone expression, revealing a transcriptional instability associated with aging. By further analyzing the spectrum of somatic mutations in single cells, we found a specific age-dependent mutational signature characterized by C to A and C to G transversions. These mutations are indicators of oxidative stress and the signature is absent in single cells from human brain tissue or in a tumor cell line. We have used the single cell measurements of transcriptional noise and mutation level to identify molecular pathways correlated with these changes that could influence human disease. Our results demonstrate the feasibility of using single-cell RNA-seq data from primary cells to derive meaningful insights into the genetic processes that operate on aging human tissue and to determine molecular mechanisms coordinated with these processes.

scholarly journals A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carla A. Gonçalves ◽  
Michael Larsen ◽  
Sascha Jung ◽  
Johannes Stratmann ◽  
Akiko Nakamura ◽  
...  
Keyword(s):  
Single Cell ◽  
R Package ◽  
Fetal Tissue ◽  
Defined Medium ◽  
Three Dimensions ◽  
Practical Reasons ◽  
Human Pancreas ◽  
Fetal Pancreas ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractHuman organogenesis remains relatively unexplored for ethical and practical reasons. Here, we report the establishment of a single-cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell–cell interactions, we describe InterCom, an R-Package we developed for identifying receptor–ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2-dimensions and those expanded in 3-dimensions to fetal tissue identifies that progenitors expanded in 3-dimensions are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion.

scholarly journals Single cell transcriptome atlas of mouse mammary epithelial cells across development

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Bhupinder Pal ◽  
Yunshun Chen ◽  
Michael J. G. Milevskiy ◽  
François Vaillant ◽  
Lexie Prokopuk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Developmental Stages ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Single Cells ◽  
Chromatin Accessibility ◽  
Mammary Epithelial ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.

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