scholarly journals A transposon expression burst accompanies the activation of Y-chromosome fertility genes during Drosophila spermatogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthew A. Lawlor ◽  
Weihuan Cao ◽  
Christopher E. Ellison

AbstractTransposable elements (TEs) must replicate in germline cells to pass novel insertions to offspring. In Drosophila melanogaster ovaries, TEs can exploit specific developmental windows of opportunity to evade host silencing and increase their copy numbers. However, TE activity and host silencing in the distinct cell types of Drosophila testis are not well understood. Here, we reanalyze publicly available single-cell RNA-seq datasets to quantify TE expression in the distinct cell types of the Drosophila testis. We develop a method for identification of TE and host gene expression modules and find that a distinct population of early spermatocytes expresses a large number of TEs at much higher levels than other germline and somatic components of the testes. This burst of TE expression coincides with the activation of Y chromosome fertility factors and spermatocyte-specific transcriptional regulators, as well as downregulation of many components of the piRNA pathway. The TEs expressed by this cell population are specifically enriched on the Y chromosome and depleted on the X chromosome, relative to other active TEs. These data suggest that some TEs may achieve high insertional activity in males by exploiting a window of opportunity for mobilization created by the activation of spermatocyte-specific and Y chromosome-specific transcriptional programs.

2021 ◽  
Author(s):  
Matthew A Lawlor ◽  
Weihuan Cao ◽  
Christopher E Ellison

Transposable elements (TEs) must replicate in germline cells to pass novel insertions to offspring. In Drosophila melanogaster ovaries, TEs can exploit specific developmental windows of opportunity to evade host silencing and increase their copy numbers. However, TE activity and host silencing in the distinct cell types of the Drosophila melanogaster testis are not well understood. We reanalyzed publicly available single-cell RNA-seq datasets to quantify TE expression in the distinct cell types of the Drosophila testis. We developed a novel method for identification of TE and host gene expression programs and find that a distinct population of early spermatocytes expresses a large number of TEs at much higher levels than other germline and somatic components of the testes. This burst of TE expression coincides with the activation of Y chromosome fertility factors and spermatocyte-specific transcriptional regulators, as well as downregulation of many components of the piRNA pathway. The TEs expressed by this cell population are enriched on the Y chromosome and depleted on the X chromosome relative to other active TEs. These data suggest that some TEs may achieve high insertional activity in males by exploiting a window of opportunity for mobilization created by the activation of spermatocyte-specific and Y-chromosome-specific transcriptional programs.


2020 ◽  
Author(s):  
Jixing Zhong ◽  
Gen Tang ◽  
Jiacheng Zhu ◽  
Xin Qiu ◽  
Weiying Wu ◽  
...  

AbstractParkinson’s disease (PD) is a neurodegenerative disease leading to the impairment of execution of movement. PD pathogenesis has been largely investigated, but either restricted in bulk level or at certain cell types, which failed to capture cellular heterogeneity and intrinsic interplays among distinct cell types. To overcome this, we applied single-nucleus RNA-seq and single cell ATAC-seq on cerebellum, midbrain and striatum of PD mouse and matched control. With 74,493 cells in total, we comprehensively depicted the dysfunctions under PD pathology covering proteostasis, neuroinflammation, calcium homeostasis and extracellular neurotransmitter homeostasis. Besides, by multi-omics approach, we identified putative biomarkers for early stage of PD, based on the relationships between transcriptomic and epigenetic profiles. We located certain cell types that primarily contribute to PD early pathology, narrowing the gap between genotypes and phenotypes. Taken together, our study provides a valuable resource to dissect the molecular mechanism of PD pathogenesis at single cell level, which could facilitate the development of novel methods regarding diagnosis, monitoring and practical therapies against PD at early stage.


2021 ◽  
Author(s):  
Qi Sun ◽  
YIFAN PENG ◽  
Jinze Liu

The single-cell RNA sequencing (scRNA-seq) has become a revolutionary technology to detect and characterize distinct cell populations under different biological conditions. Unlike bulk RNA-seq, the expression of genes from scRNA-seq is highly sparse due to limited sequencing depth per cell. This is worsened by tossing away a significant portion of reads that cannot be mapped during gene quantification. To overcome data sparsity and fully utilize original sequences, we propose scSimClassify, a reference-free and alignment-free approach to classify cell types with k-mer level features derived from raw reads in a scRNA-seq experiment. The major contribution of scSimClassify is the simhash method compressing k-mers with similar abundance profiles into groups. The compressed k-mer groups (CKGs) serve as the aggregated k-mer level features for cell type classification. We evaluate the performance of CKG features for predicting cell types in four scRNA-seq datasets comparing four state-of-the-art classification methods as well as two scRNA-seq specific algorithms. Our experiments demonstrate that the CKG features lend themselves to better performance than traditional gene expression features in scRNA-seq classification accuracy in the majority of cases. Because CKG features can be efficiently derived from raw reads without a resource-intensive alignment process, scSimClassify offers an efficient alternative to help scientists rapidly classify cell types without relying on reference sequences. The current version of scSimClassify is implemented in python and can be found at https://github.com/digi2002/scSimClassify.


2018 ◽  
Author(s):  
Erica A.K. DePasquale ◽  
Daniel J. Schnell ◽  
Íñigo Valiente-Alandí ◽  
Burns C. Blaxall ◽  
H. Leighton Grimes ◽  
...  

SUMMARYMethods for single-cell RNA sequencing (scRNA-Seq) have greatly advanced in recent years. While droplet- and well-based methods have increased the capture frequency of cells for scRNA-Seq, these technologies readily produce technical artifacts, such as doublet-cell and multiplet-cell captures. Doublets occurring between distinct cell-types can appear as hybrid scRNA-Seq profiles, but do not have distinct transcriptomes from individual cell states. We introduce DoubletDecon, an approach that detects doublets with a combination of deconvolution analyses and the identification of unique cell-state gene expression. We demonstrate the ability of DoubletDecon to identify synthetic and cell-hashing cell singlets and doublets from scRNA-Seq datasets of varying cellular complexity. DoubletDecon is able to account for cell-cycle effects and is compatible with diverse species and unsupervised population detection algorithms (e.g., ICGS, Seurat). We believe this approach has the potential to become a standard quality control step for the accurate delineation of cell states.


2020 ◽  
Author(s):  
Deepthi Y Tulasi ◽  
Diego Martinez Castaneda ◽  
Kortney Wager ◽  
Karel P Alcedo ◽  
Jesse R Raab ◽  
...  

ABSTRACTIntrahepatic bile ducts are lined by biliary epithelial cells (BECs). However, defining the genetic heterogeneity of BECs remains challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize Sox9EGFP transgene expression in the liver and demonstrate that GFP expression levels are associated with distinct cell types. BECs express “low” or “high” levels of GFP, while periportal hepatocytes express “sublow” GFP. Sox9EGFP distribution varies by duct size, with GFPhigh BECs found at greater numbers in smaller ducts. RNA-seq reveals distinct gene expression signatures for Sox9EGFP populations and enrichment of Notch and Yap signaling in GFPlow and GFPhigh BECs. All GFP+ populations are capable of forming organoids, but demonstrate interpopulation differences in organoid survival and size, dependent on media conditions. Organoids derived from Sox9EGFP populations also demonstrate differential activation of HNF4A protein in hepatocyte media conditions, suggesting variable potency in BEC subpopulations. We find that Yap signaling is required to maintain Sox9 expression in biliary organoids, and that bile acids are insufficient to induce Yap activity or Sox9 in vivo and in vitro. Our data demonstrate that Sox9EGFP levels provide a readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.


2021 ◽  
Author(s):  
Sanjeeva S Metikala ◽  
Satish Casie Chetty ◽  
Saulius Sumanas

During embryonic development, cells differentiate into a variety of distinct cell types and subtypes with diverse transcriptional profiles. To date, transcriptomic signatures of different cell lineages that arise during development have been only partially characterized. Here we used single-cell RNA-seq to perform transcriptomic analysis of over 20,000 cells disaggregated from the trunk region of zebrafish embryos at the 30 hpf stage. Transcriptional signatures of 27 different cell types and subtypes were identified and annotated during this analysis. This dataset will be a useful resource for many researchers in the fields of developmental and cellular biology and facilitate the understanding of molecular mechanisms that regulate cell lineage choices during development.


2019 ◽  
Author(s):  
Jacob C. Kimmel ◽  
Lolita Penland ◽  
Nimrod D. Rubinstein ◽  
David G. Hendrickson ◽  
David R. Kelley ◽  
...  

AbstractBackgroundAging is a pleiotropic process affecting many aspects of organismal and cellular physiology. Mammalian organisms are composed of a constellation of distinct cell type and state identities residing within different tissue environments. Due to technological limitations, the study of aging has traditionally focused on changes within individual cell types, or the aggregate changes across cell types within a tissue. The influence of cell identity and tissue environment on the trajectory of aging therefore remains unclear.ResultsHere, we perform single cell RNA-seq on >50,000 individual cells across three tissues in young and aged mice. These molecular profiles allow for comparison of aging phenotypes across cell types and tissue environments. We find transcriptional features of aging common across many cell types, as well as features of aging unique to each type. Leveraging matrix factorization and optimal transport methods, we compute a trajectory and magnitude of aging for each cell type. We find that cell type exerts a larger influence on these measures than tissue environment.ConclusionIn this study, we use single cell RNA-seq to dissect the influence of cell identity and tissue environment on the aging process. Single cell analysis reveals that cell identities age in unique ways, with some common features of aging shared across identities. We find that both cell identities and tissue environments exert influence on the trajectory and magnitude of aging, with cell identity influence predominating. These results suggest that aging manifests with unique directionality and magnitude across the diverse cell identities in mammals.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254024
Author(s):  
Sanjeeva Metikala ◽  
Satish Casie Chetty ◽  
Saulius Sumanas

During embryonic development, cells differentiate into a variety of distinct cell types and subtypes with diverse transcriptional profiles. To date, transcriptomic signatures of different cell lineages that arise during development have been only partially characterized. Here we used single-cell RNA-seq to perform transcriptomic analysis of over 20,000 cells disaggregated from the trunk region of zebrafish embryos at the 30 hpf stage. Transcriptional signatures of 27 different cell types and subtypes were identified and annotated during this analysis. This dataset will be a useful resource for many researchers in the fields of developmental and cellular biology and facilitate the understanding of molecular mechanisms that regulate cell lineage choices during development.


Author(s):  
Brendan Clifford

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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Que ◽  
David Lukacsovich ◽  
Wenshu Luo ◽  
Csaba Földy

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.


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