scholarly journals spicyR: Spatial analysis of in situ cytometry data in R

2021 ◽  
Author(s):  
Nicolas Paolo Canete ◽  
Sourish Suresh Iyengar ◽  
John T Ormerod ◽  
Andrew N Harman ◽  
Ellis Patrick
Keyword(s):  
Spatial Analysis ◽  
Disease Process ◽  
Simulated Data ◽  
High Sensitivity ◽  
Cell Types ◽  
R Package ◽  
Comprehensive Overview ◽  
Histological Techniques ◽  
Disease States ◽  
Distinct Cell

Motivation: High parameter histological techniques have allowed for the identification of a variety of distinct cell types within an image, providing a comprehensive overview of the tissue environment. This allows the complex cellular architecture and environment of diseased tissue to be explored. While spatial analysis techniques have revealed how cell-cell interactions are important within the disease pathology, there remains a gap in exploring changes in these interactions within the disease process. Specifically, there are currently no established methods for performing inference on cell localisation changes across images, hindering an understanding of how cellular environments change with a disease pathology. Results: We have developed the spicyR R package to perform inference on changes in the spatial localisation of cell types across groups of images. Application to simulated data demonstrates a high sensitivity and specificity. We demonstrate the utility of spicyR by applying it to a type 1 diabetes imaging mass cytometry dataset, revealing changes in cellular associations that were relevant to the disease progression. Ultimately, spicyR allows changes in cellular environments to be explored under different pathologies or disease states.

Clinical relevance of the neurotrophins and their receptors

2006 ◽  
Vol 110 (2) ◽  
pp. 175-191 ◽  
Author(s):  
Shelley J. Allen ◽  
David Dawbarn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Disease Process ◽  
Neuronal Cell ◽  
Cell Types ◽  
Dependent Manner ◽  
Disease States ◽  
Neuronal Tissues

The neurotrophins are growth factors required by discrete neuronal cell types for survival and maintenance, with a broad range of activities in the central and peripheral nervous system in the developing and adult mammal. This review examines their role in diverse disease states, including Alzheimer's disease, depression, pain and asthma. In addition, the role of BDNF (brain-derived neurotrophic factor) in synaptic plasticity and memory formation is discussed. Unlike the other neurotrophins, BDNF is secreted in an activity-dependent manner that allows the highly controlled release required for synaptic regulation. Evidence is discussed which shows that sequestration of NGF (nerve growth factor) is able to reverse symptoms of inflammatory pain and asthma in animal models. Both pain and asthma show an underlying pathophysiology linked to increases in endogenous NGF and subsequent NGF-dependent increase in BDNF. Conversely, in Alzheimer's disease, there is a role for NGF in the treatment of the disease and a recent clinical trial has shown benefit from its exogenous application. In addition, reductions in BDNF, and changes in the processing and usage of NGF, are evident and it is possible that both NGF and BDNF play a part in the aetiology of the disease process. This highly selective choice of functions and disease states related to neurotrophin function, although in no way comprehensive, illustrates the importance of the neurotrophins in the brain, the peripheral nervous system and in non-neuronal tissues. Ways in which the neurotrophins, their receptors or agonists/antagonists may act therapeutically are discussed.

CHANGES IN ADENOHYPOPHYSEAL CYTOLOGY AND NUCLEIC ACID CONTENT IN THE RAT 32 DAYS AFTER BILATERAL ADRENALECTOMY AND THE CHRONIC INJECTION OF CORTISOL

1967 ◽  
Vol 45 (6) ◽  
pp. 947-956 ◽  
Author(s):  
Jacob Kraicer ◽  
Marc Herlant ◽  
Pierre Duclos
Keyword(s):  
Cell Types ◽  
Bilateral Adrenalectomy ◽  
Synthetic Activity ◽  
Nucleic Acid Content ◽  
Cell Type ◽  
Cytological Evidence ◽  
Histological Techniques ◽  
Dna And Rna ◽  
Distinct Cell ◽  
Chronic Injection

Control, adrenalectomized, and cortisol-treated rats were maintained under rigidly controlled conditions, and the adenohypophyses were examined histologically with two staining procedures which differentiate six distinct cell types. Only one cell type demonstrated cytological evidence of increased synthetic activity 32 days after adrenalectomy (the changes were, however, minimal) and decreased synthetic activity following the chronic injection of cortisol. This cell type, which we designate as the corticotroph, would be classed as a chromophobe (no stainable granules) with use of standard histological techniques, but is, in fact, as Herlant's Tetrachrome demonstrates, a distinct acidophilic cell type different from the prolactin cell and the somatotroph. The determination of adenohypophyseal DNA and RNA revealed no evidence of increased protein synthetic activity following bilateral adrenalectomy, but did reveal evidence of decreased protein synthetic activity following the chronic injection of cortisol.

scholarly journals Cell-specific characterization of the placental methylome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria S. Peñaherrera ◽  
Alexander G. Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare understudied macrophage population thought to derive from fetal monocytes. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals AI-driven Deep Visual Proteomics defines cell identity and heterogeneity

2021 ◽  
Author(s):  
Andreas Mund ◽  
Fabian Coscia ◽  
Réka Hollandi ◽  
Ferenc Kovács ◽  
András Kriston ◽  
...  
Keyword(s):  
Single Cell ◽  
Spatial Information ◽  
High Sensitivity ◽  
Cell Types ◽  
Cellular Function ◽  
Disease Biology ◽  
Specific Tumor ◽  
Distinct Cell ◽  
Rare Cells ◽  
Cellular Phenotypes

ABSTRACTThe systems-wide analysis of biomolecules in time and space is key to our understanding of cellular function and heterogeneity in health and disease1. Remarkable technological progress in microscopy and multi-omics technologies enable increasingly data-rich descriptions of tissue heterogeneity2,3,4,5. Single cell sequencing, in particular, now routinely allows the mapping of cell types and states uncovering tremendous complexity6. Yet, an unaddressed challenge is the development of a method that would directly connect the visual dimension with the molecular phenotype and in particular with the unbiased characterization of proteomes, a close proxy for cellular function. Here we introduce Deep Visual Proteomics (DVP), which combines advances in artificial intelligence (AI)-driven image analysis of cellular phenotypes with automated single cell laser microdissection and ultra-high sensitivity mass spectrometry7. DVP links protein abundance to complex cellular or subcellular phenotypes while preserving spatial context. Individually excising nuclei from cell culture, we classified distinct cell states with proteomic profiles defined by known and novel proteins. AI also discovered rare cells with distinct morphology, whose potential function was revealed by proteomics. Applied to archival tissue of salivary gland carcinoma, our generic workflow characterized proteomic differences between normal-appearing and adjacent cancer cells, without admixture of background from unrelated cells or extracellular matrix. In melanoma, DVP revealed immune system and DNA replication related prognostic markers that appeared only in specific tumor regions. Thus, DVP provides unprecedented molecular insights into cell and disease biology while retaining spatial information.

Fine Structure of the Malpighian Tubules of the Mosquito, Culex pipiens

1971 ◽  
Vol 29 ◽  
pp. 402-403
Author(s):  
Brendan Clifford
Keyword(s):  
Fine Structure ◽  
Culex Pipiens ◽  
Stellate Cell ◽  
Malpighian Tubule ◽  
Cell Types ◽  
Instar Larva ◽  
Malpighian Tubules ◽  
Calliphora Erythrocephala ◽  
Distinct Cell ◽  
Basal Plasma

An ultrastructural investigation of the Malpighian tubules of the fourth instar larva of Culex pipiens was undertaken as part of a continuing study of the fine structure of transport epithelia.Each of the five Malpighian tubules was found to be morphologically identical and regionally undifferentiated. Two distinct cell types, the primary and stellate, were found intermingled along the length of each tubule. The ultrastructure of the stellate cell was previously described in the Malpighian tubule of the blowfly, Calliphora erythrocephala by Berridge and Oschman.The basal plasma membrane of the primary cell is extremely irregular, giving rise to a complex interconnecting network of basal channels. The compartments of cytoplasm entrapped within this system of basal infoldings contain mitochondria, free ribosomes, and small amounts of rough endoplasmic reticulum. The mitochondria are distinctive in that the cristae run parallel to the long axis of the organelle.

The Concepts of Prevalence and Incidence as Applied to the Study of Development and Duration of Disease

1968 ◽  
Vol 7 (02) ◽  
pp. 111-117 ◽  
Author(s):  
M. Kashgahian
Keyword(s):  
Mass Screening ◽  
Disease Process ◽  
Incidence Data ◽  
Disease States ◽  
History Of ◽  
Duration Of Disease ◽  
Process Methodology

The proper use of prevalence and incidence data can result in an effective way to study the history of the disease process. Methodology is given whereby the progression, duration and transition of diseases can be elucidated. Prevalence and incidence have been redefined and used in an unconventional way in view of new types of data which are being generated by mass screening projects for disease which are able to discover presymptomatic and preclinical disease states.

scholarly journals NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 355
Author(s):  
Guilhem Lalle ◽  
Julie Twardowski ◽  
Yenkel Grinberg-Bleyer
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Transcriptional Activators ◽  
New Class ◽  
Complex Interactions ◽  
Cancer Immunity ◽  
Distinct Cell ◽  
Cancer Initiation ◽  
Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

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