scholarly journals Transcription activation of early human development suggests DUX4 as an embryonic regulator

2017 ◽  
Author(s):  
Virpi Töhönen ◽  
Shintaro Katayama ◽  
Liselotte Vesterlund ◽  
Mona Sheikhi ◽  
Liselotte Antonsson ◽  
...  
Keyword(s):  
Single Cells ◽  
Homeobox Gene ◽  
Cell Types ◽  
Cell Type ◽  
Cell Stage ◽  
Repeat Elements ◽  
Telomere Elongation ◽  
Distinct Cell ◽  
Cell Embryo ◽  
Gene Transcripts

In order to better understand human preimplantation development we applied massively parallel RNA sequencing on 337 single cells from oocytes up to 8-cell embryo blastomeres. Surprisingly, already before zygote pronuclear fusion we observed drastic changes in the transcriptome compared to the unfertilized egg: 1,804 gene transcripts and 32 repeat elements become more abundant, among these the double-homeobox geneDUX4. Several genes previously identified asDUX4targets, such asCCNA1, KHDC1LandZSCAN4, as well as several members of theRFPLs, TRIMSandPRAMEFs1were accumulated in 4-cell stage blastomeres, suggestingDUX4as an early regulator. In the 8-cell stage, we observed two distinct cell types – a transcript-poor cell type, and a transcript-rich cell type with many Alu repeats and accumulated markers for pluripotency and stemness, telomere elongation and growth. In summary, this unprecedented detailed view of the first three days of human embryonic development reveals more complex changes in the transcriptome than what was previously known.

scholarly journals Initial Cell Type Choice in Dictyostelium

2010 ◽  
Vol 10 (2) ◽  
pp. 150-155 ◽  
Author(s):  
Wonhee Jang ◽  
Richard H. Gomer
Keyword(s):  
Single Cells ◽  
Cell Types ◽  
Break Symmetry ◽  
Stalk Cell ◽  
Cycle Phase ◽  
Cell Type ◽  
Content Type ◽  
Initial Cell ◽  
Distinct Cell ◽  
A Cell

ABSTRACT Much remains to be understood about how a group of cells break symmetry and differentiate into distinct cell types. The simple eukaryote Dictyostelium discoideum is an excellent model system for studying questions such as cell type differentiation. Dictyostelium cells grow as single cells. When the cells starve, they aggregate to develop into a multicellular structure with only two main cell types: spore and stalk. There has been a longstanding controversy as to how a cell makes the initial choice of becoming a spore or stalk cell. In this review, we describe how the controversy arose and how a consensus developed around a model in which initial cell type choice in Dictyostelium is dependent on the cell cycle phase that a cell happens to be in at the time that it starves.

Distribution of microvilli on dissociated blastomeres from mouse embryos: evidence for surface polarization at compaction

Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 339-350
Author(s):  
W. J. D. Reeve ◽  
C. A. Ziomek
Keyword(s):  
Ligand Binding ◽  
Single Cells ◽  
Progressive Increase ◽  
Mouse Embryos ◽  
Cell Stage ◽  
Characteristic Distribution ◽  
Surface Polarization ◽  
Cell Embryo ◽  
Fluorescent Ligand ◽  
Scanning Electron

Cells of mouse embryos develop a polarization of microvillous distribution at compaction. Cells of the 4-cell embryo show a uniform pattern of fluorescent-ligand binding and an even distribution of microvilli. Each cell of the early 8-cell embryo has a uniform distribution both of microvilli and of fluorescent ligand. During the 8-cell stage, there is a progressive increase in the incidence of cells which show microvilli restricted to a region normally on the exposed surface of the embryo. When late 8-cell embryos were disaggregated to single cells, and these sorted by pattern of fluorescent-ligand binding, each of the four patterns of staining related consistently to a characteristic distribution of microvilli as viewed by scanning electron microscopy. The 16-cell embryo possessed an inside population of uniformly labelled cells with a sparse microvillous distribution, and an outside population of cells, each of which had a microvillous pole.

scholarly journals Genomic Architecture of Cells in Tissues (GeACT): Study of Human Mid-gestation Fetus

2020 ◽  
Author(s):  
Feng Tian ◽  
Fan Zhou ◽  
Xiang Li ◽  
Wenping Ma ◽  
Honggui Wu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Human Cell ◽  
Expression Profiles ◽  
Single Cells ◽  
Cell Types ◽  
List Type ◽  
Cell Type ◽  
Genomic Architecture ◽  
Gene Modules

SummaryBy circumventing cellular heterogeneity, single cell omics have now been widely utilized for cell typing in human tissues, culminating with the undertaking of human cell atlas aimed at characterizing all human cell types. However, more important are the probing of gene regulatory networks, underlying chromatin architecture and critical transcription factors for each cell type. Here we report the Genomic Architecture of Cells in Tissues (GeACT), a comprehensive genomic data base that collectively address the above needs with the goal of understanding the functional genome in action. GeACT was made possible by our novel single-cell RNA-seq (MALBAC-DT) and ATAC-seq (METATAC) methods of high detectability and precision. We exemplified GeACT by first studying representative organs in human mid-gestation fetus. In particular, correlated gene modules (CGMs) are observed and found to be cell-type-dependent. We linked gene expression profiles to the underlying chromatin states, and found the key transcription factors for representative CGMs.HighlightsGenomic Architecture of Cells in Tissues (GeACT) data for human mid-gestation fetusDetermining correlated gene modules (CGMs) in different cell types by MALBAC-DTMeasuring chromatin open regions in single cells with high detectability by METATACIntegrating transcriptomics and chromatin accessibility to reveal key TFs for a CGM

scholarly journals CCPLS reveals cell-type-specific spatial dependence of transcriptomes in single cells

2022 ◽  
Author(s):  
Takaho Tsuchiya ◽  
Hiroki Hori ◽  
Haruka Ozaki
Keyword(s):  
Gene Expression ◽  
Single Cells ◽  
Cell Types ◽  
Regression Modeling ◽  
Transcriptome Data ◽  
Cell Type ◽  
Neighboring Cell ◽  
Expression Variability ◽  
Cell Expression ◽  
Cell Cell

Motivation: Cell-cell communications regulate internal cellular states of the cell, e.g., gene expression and cell functions, and play pivotal roles in normal development and disease states. Furthermore, single-cell RNA sequencing methods have revealed cell-to-cell expression variability of highly variable genes (HVGs), which is also crucial. Nevertheless, the regulation on cell-to-cell expression variability of HVGs via cell-cell communications is still unexplored. The recent advent of spatial transcriptome measurement methods has linked gene expression profiles to the spatial context of single cells, which has provided opportunities to reveal those regulations. The existing computational methods extract genes with expression levels that are influenced by neighboring cell types based on the spatial transcriptome data. However, limitations remain in the quantitativeness and interpretability: it neither focuses on HVGs, considers cooperation of neighboring cell types, nor quantifies the degree of regulation with each neighboring cell type. Results: Here, we propose CCPLS (Cell-Cell communications analysis by Partial Least Square regression modeling), which is a statistical framework for identifying cell-cell communications as the effects of multiple neighboring cell types on cell-to-cell expression variability of HVGs, based on the spatial transcriptome data. For each cell type, CCPLS performs PLS regression modeling and reports coefficients as the quantitative index of the cell-cell communications. Evaluation using simulated data showed our method accurately estimated effects of multiple neighboring cell types on HVGs. Furthermore, by applying CCPLS to the two real datasets, we demonstrate CCPLS can be used to extract biologically interpretable insights from the inferred cell-cell communications.

scholarly journals A nervous system-specific subnuclear organelle in Caenorhabditis elegans

Genetics ◽  
2021 ◽  
Vol 217 (1) ◽  
Author(s):  
Kenneth Pham ◽  
Neda Masoudi ◽  
Eduardo Leyva-Díaz ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Homeobox Gene ◽  
Cell Types ◽  
Nuclear Bodies ◽  
Loss Of Function ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Splicing Speckles ◽  
Polycomb Bodies

Abstract We describe here phase-separated subnuclear organelles in the nematode Caenorhabditis elegans, which we term NUN (NUclear Nervous system-specific) bodies. Unlike other previously described subnuclear organelles, NUN bodies are highly cell type specific. In fully mature animals, 4–10 NUN bodies are observed exclusively in the nucleus of neuronal, glial and neuron-like cells, but not in other somatic cell types. Based on co-localization and genetic loss of function studies, NUN bodies are not related to other previously described subnuclear organelles, such as nucleoli, splicing speckles, paraspeckles, Polycomb bodies, promyelocytic leukemia bodies, gems, stress-induced nuclear bodies, or clastosomes. NUN bodies form immediately after cell cycle exit, before other signs of overt neuronal differentiation and are unaffected by the genetic elimination of transcription factors that control many other aspects of neuronal identity. In one unusual neuron class, the canal-associated neurons, NUN bodies remodel during larval development, and this remodeling depends on the Prd-type homeobox gene ceh-10. In conclusion, we have characterized here a novel subnuclear organelle whose cell type specificity poses the intriguing question of what biochemical process in the nucleus makes all nervous system-associated cells different from cells outside the nervous system.

scholarly journals A computational method to aid the design and analysis of single cell RNA-seq experiments for cell type identification

2018 ◽  
Author(s):  
Douglas Abrams ◽  
Parveen Kumar ◽  
R. Krishna Murthy Karuturi ◽  
Joshy George
Keyword(s):  
Experimental Design ◽  
Single Cell ◽  
Single Cells ◽  
Cell Types ◽  
Cell Number ◽  
Fold Change ◽  
Computational Method ◽  
Marker Genes ◽  
Cell Type ◽  
Estimate Sample Size

AbstractBackgroundThe advent of single cell RNA sequencing (scRNA-seq) enabled researchers to study transcriptomic activity within individual cells and identify inherent cell types in the sample. Although numerous computational tools have been developed to analyze single cell transcriptomes, there are no published studies and analytical packages available to guide experimental design and to devise suitable analysis procedure for cell type identification.ResultsWe have developed an empirical methodology to address this important gap in single cell experimental design and analysis into an easy-to-use tool called SCEED (Single Cell Empirical Experimental Design and analysis). With SCEED, user can choose a variety of combinations of tools for analysis, conduct performance analysis of analytical procedures and choose the best procedure, and estimate sample size (number of cells to be profiled) required for a given analytical procedure at varying levels of cell type rarity and other experimental parameters. Using SCEED, we examined 3 single cell algorithms using 48 simulated single cell datasets that were generated for varying number of cell types and their proportions, number of genes expressed per cell, number of marker genes and their fold change, and number of single cells successfully profiled in the experiment.ConclusionsBased on our study, we found that when marker genes are expressed at fold change of 4 or more than the rest of the genes, either Seurat or Simlr algorithm can be used to analyze single cell dataset for any number of single cells isolated (minimum 1000 single cells were tested). However, when marker genes are expected to be only up to fC 2 upregulated, choice of the single cell algorithm is dependent on the number of single cells isolated and proportion of rare cell type to be identified. In conclusion, our work allows the assessment of various single cell methods and also aids in examining the single cell experimental design.

Cell lineage in marine nematode Enoplus brevis

Development ◽  
1998 ◽  
Vol 125 (1) ◽  
pp. 143-150
Author(s):  
D.A. Voronov ◽  
Y.V. Panchin
Keyword(s):  
Fluorescent Dyes ◽  
Cell Lineage ◽  
Cell Types ◽  
Ventral Side ◽  
Marine Nematode ◽  
Cell Stage ◽  
Cell Embryo ◽  
Multiple Cell ◽  
Nerve Muscle ◽  
Nematode Development

Early cleavages of the marine nematode Enoplus brevis are symmetrical and occur in synchrony. At the 2- to 16-cell stages, blastomeres are indistinguishable. The progeny of blastomeres was investigated by intracellular injections of fluorescent dyes and horse radish peroxidase. One blastomere of the 2-cell embryo gives rise to a compact group of cells occupying about half of an embryo. The border between labeled and unlabeled cells differs in each embryo dividing it to anterior-posterior, left-right or intermediate parts. At the 8-cell stage, one blastomere gives rise to only endoderm, whereas the other blastomeres produce progeny that form multiple cell types, including nerve, muscle and hypoderm cells, in various proportions. Thus the fates of the blastomeres of early E. brevis embryos, with the exception of the endoderm precursor, are not determined. The process of gastrulation in E. brevis is very similar to that in Caenorhabditis elegans and other nematodes. At the beginning of gastrulation, the 2-celled endoderm precursor lies on the surface of embryo and then sinks inwards. After labeling of cells on the ventral side (near endoderm precursor) at the beginning of gastrulation, their progeny differentiate predominantly into body muscles or pharyngeal cells of the first stage larva. Cells that are located more laterally give rise mainly to neurons. The dorsal blastomeres differentiated principally into hypoderm cells. Our study suggests that a precise cell lineage is not a necessary attribute of nematode development.

scholarly journals Independent glial subtypes delay development and extend healthy lifespan upon reduced insulin-PI3K signalling

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Nathaniel S. Woodling ◽  
Arjunan Rajasingam ◽  
Lucy J. Minkley ◽  
Alberto Rizzo ◽  
Linda Partridge
Keyword(s):  
Glial Cell ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Developmental Timing ◽  
Cell Type ◽  
Specific Effects ◽  
Trade Offs ◽  
Distinct Cell ◽  
Pi3k Signalling ◽  
Cell Type Specific

Abstract Background The increasing age of global populations highlights the urgent need to understand the biological underpinnings of ageing. To this end, inhibition of the insulin/insulin-like signalling (IIS) pathway can extend healthy lifespan in diverse animal species, but with trade-offs including delayed development. It is possible that distinct cell types underlie effects on development and ageing; cell-type-specific strategies could therefore potentially avoid negative trade-offs when targeting diseases of ageing, including prevalent neurodegenerative diseases. The highly conserved diversity of neuronal and non-neuronal (glial) cell types in the Drosophila nervous system makes it an attractive system to address this possibility. We have thus investigated whether IIS in distinct glial cell populations differentially modulates development and lifespan in Drosophila. Results We report here that glia-specific IIS inhibition, using several genetic means, delays development while extending healthy lifespan. The effects on lifespan can be recapitulated by adult-onset IIS inhibition, whereas developmental IIS inhibition is dispensable for modulation of lifespan. Notably, the effects we observe on both lifespan and development act through the PI3K branch of the IIS pathway and are dependent on the transcription factor FOXO. Finally, IIS inhibition in several glial subtypes can delay development without extending lifespan, whereas the same manipulations in astrocyte-like glia alone are sufficient to extend lifespan without altering developmental timing. Conclusions These findings reveal a role for distinct glial subpopulations in the organism-wide modulation of development and lifespan, with IIS in astrocyte-like glia contributing to lifespan modulation but not to developmental timing. Our results enable a more complete picture of the cell-type-specific effects of the IIS network, a pathway whose evolutionary conservation in humans make it tractable for therapeutic interventions. Our findings therefore underscore the necessity for cell-type-specific strategies to optimise interventions for the diseases of ageing.

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 Multimodal cell type correspondence by intersectional mFISH in intact tissues

2019 ◽  
Author(s):  
Philip R. Nicovich ◽  
Michael J. Taormina ◽  
Christopher A. Baker ◽  
Thuc Nghi Nguyen ◽  
Elliot R. Thomsen ◽  
...  
Keyword(s):  
Single Cells ◽  
Morphological Characteristics ◽  
Cell Types ◽  
Synaptic Connectivity ◽  
Cell Type ◽  
New Approach ◽  
Two Photon ◽  
Mouse Cortex ◽  
Complete Set

AbstractDefining a complete set of cell types within the cortex requires reconciling disparate results achieved through diverging methodologies. To address this correspondence problem, multiple methodologies must be applied to the same cells across multiple single-cell experiments. Here we present a new approach applying spatial transcriptomics using multiplexed fluorescencein situhybridization, (mFISH) to brain tissue previously interrogated through two photon optogenetic mapping of synaptic connectivity. This approach can resolve the anatomical, transcriptomic, connectomic, electrophysiological, and morphological characteristics of single cells within the mouse cortex.

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