Single cell transcriptomic and spatial landscapes of the developing human pancreas

Olaniru, Oladapo E.; Kadolsky, Ulrich D.; Kannambath, Shichina; Vaikkinen, Heli; Fung, Kathy; Dhami, Pawan; Persaud, Shanta J.

doi:10.1101/2022.02.04.478971

Cited by 3 publications

(19 citation statements)

References 73 publications

(106 reference statements)

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“…Spatial transcriptomics is a powerful technique that is used to resolve cellular trajectories occurring in situ and because of its applicability, it was named ‘Method of the Year’ in 2020 33 . Several versions of spatial transcriptomics have been developed and they vary in throughput and resolution, including Visium, Tomo‐Seq and GeoMx Digital Spatial Profiling, 34 but only Visium has been used to study human fetal pancreas, to the best of our knowledge 11 …”

Section: Spatial Transcriptomicsmentioning

confidence: 99%

“…33 Several versions of spatial transcriptomics have been developed and they vary in throughput and resolution, including Visium, Tomo-Seq and GeoMx Digital Spatial Profiling, 34 but only Visium has been used to study human fetal pancreas, to the best of our knowledge. 11 Visium spatial transcriptomics by 10× Genomics combines histology with the quantitative spatial distribution of transcripts across tissue samples to reveal cellular heterogeneity and positional gene patterns. 35 Fresh frozen or formalin-fixed paraffin-embedded (FFPE) sections are mounted on spatial slides and for successful assessment of the spatial organisation, care must be taken during sectioning and mounting to preserve tissue morphology.…”

Section: Spatial Transcriptomicsmentioning

confidence: 99%

“…The use of scRNAseq to measure changes in the transcriptome of the human fetal pancreas over a range of gestational stages has recently allowed data mining of potential genes related to beta cell development 11,13 . In addition, these studies have provided information on pseudo‐time ordering, which has led to improved understanding of the order in which genes are expressed during pancreatic cell lineage specification 11,13 . More detailed information on the use of scRNAseq to provide wider information on pancreas development may be found in a recent review 32 …”

Section: Single‐cell Rna Sequencingmentioning

confidence: 99%

“…Cell–cell interactions within the developing human pancreas. (a) Schematic showing the spatial proximity of the different cell types identified by spatial transcriptomics of the developing human pancreas 11 . (b) Circos plot showing predicted ligand‐receptor pairs from cell–cell connectivity analysis of human fetal pancreatic cells at 12–20 PCW 11 …”

Section: Pancreatic Microenvironmentmentioning

confidence: 99%

“…However, the current protocols, which largely mimic mouse pancreas development, yield at best 30%–50% beta‐like cells, 9 require an in vivo maturation stage and the beta‐like cells generated do not yet have comparable metabolic attributes to human islets 5,10 . Recent studies using multi‐omics technologies are beginning to shed light on the molecular landscapes of the human fetal pancreas at multiple developmental stages at a single‐cell resolution 11‐14 . The detailed information obtained from profiling pancreatic progenitor cells as they differentiate and mature into beta cells over different stages of development will be of critical assistance to the global effort of producing functional beta‐like cells in vitro, which will not require additional maturation steps before clinical use.…”

Section: Introductionmentioning

confidence: 99%

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Using single‐cell multi‐omics screening of human fetal pancreas to identify novel players in human beta cell development

2022

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Islet transplantation from organ donors can considerably improve glucose homeostasis and well‐being in individuals with type 1 diabetes, where the beta cells are destroyed by the autoimmune attack, but there are insufficient donor islets to make this a widespread therapy. Strategies are therefore being developed to generate unlimited amounts of insulin‐producing beta cells from pluripotent stem cells, with the aim that they will be transplanted to treat diabetes. Whilst much progress has been made in recent years in the directed differentiation of pluripotent stem cells to beta‐like cells, essential gaps still exist in generating stem cell‐derived beta cells that are fully functional in vitro. This short review provides details of recent multi‐‘omics’ studies of the human fetal pancreas, which are revealing granular information on the various cell types in the developing pancreas. It is anticipated that this fine mapping of the pancreatic cells at single‐cell resolution will provide additional insights that can be utilised to reproducibly produce human beta cells in vitro that have the functional characteristics of beta cells within native human islets.

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Section: Spatial Transcriptomicsmentioning

confidence: 99%

Section: Spatial Transcriptomicsmentioning

confidence: 99%

Section: Single‐cell Rna Sequencingmentioning

confidence: 99%

Section: Pancreatic Microenvironmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Using single‐cell multi‐omics screening of human fetal pancreas to identify novel players in human beta cell development

2022

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Predicting the Key Regulators of Cell Identity in Human Adult Pancreas

Vanheer¹,

Schiavo

Haele

et al. 2020

Preprint

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SUMMARYCellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies key regulators of cell identity in the human adult pancreas. We predict that HEYL and JUND are active in acinar and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell-derived pancreatic cells. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity in the human adult pancreas. Furthermore, given that transcription factors are major regulators of embryo development and are often perturbed in diseases, a comprehensive understanding of how transcription factors work will be relevant in development and disease biology.HIGHLIGHTS-Reconstruction of gene regulatory networks for human adult pancreatic cell types-An interactive resource to explore and visualize gene expression and regulatory states-Predicting putative transcription factors driving pancreatic cell identity-HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively

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Integrative spatial analysis reveals a multi-layered organization of glioblastoma

Greenwald,

Darnell,

Hoefflin

et al. 2023

Preprint

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Glioma contains malignant cells in diverse states. Hypoxic regions are associated with a unique histology of pseudopalisading cells, while other regions appear to have limited histological organization, reflecting the diffuse nature of glioma cells. Here, we combine spatial transcriptomics with spatial proteomics and novel computational approaches to define glioma cellular states at high granularity and uncover their organization. We find three prominent modes of cellular organization. First, cells in any given state tend to be spatially clustered, such that tumors are composed of small local environments that are each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. Despite the unique composition of each tumor, this pairing of states remains largely consistent across tumors. Third, the pairwise interactions that we detect collectively define a global architecture composed of five layers. Hypoxia appears to drive this 5-layered organization, as it is both associated with unique states of surrounding cells and with a long-range organization that extends from the hypoxic core to the infiltrative edge of the tumor. Accordingly, tumor regions distant from any hypoxic foci and tumors that lack hypoxia such as IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of gliomas at the resolution of cellular states and highlight the role of hypoxia as a long-range tissue organizer.

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Single cell transcriptomic and spatial landscapes of the developing human pancreas

Cited by 3 publications

References 73 publications

Using single‐cell multi‐omics screening of human fetal pancreas to identify novel players in human beta cell development

Using single‐cell multi‐omics screening of human fetal pancreas to identify novel players in human beta cell development

Predicting the Key Regulators of Cell Identity in Human Adult Pancreas

Integrative spatial analysis reveals a multi-layered organization of glioblastoma

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