scholarly journals Single-cell analysis of cell fate bifurcation in the chordate Ciona

2020 ◽  
Author(s):  
Konner M. Winkley ◽  
Wendy M. Reeves ◽  
Michael T. Veeman
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Embryonic Cell ◽  
Major Mechanism ◽  
Divergent Gene ◽  
Distinct Cell ◽  
Hourglass Model ◽  
Almost All

AbstractInductive signaling interactions between different cell types are a major mechanism for the further diversification of embryonic cell fates. Most blastomeres in the model chordate Ciona robusta become restricted to a single predominant fate between the 64-cell and mid-gastrula stages. We used single-cell RNAseq spanning this period to identify 53 distinct cell states, 25 of which are dependent on a MAPK-mediated signal critical to early Ciona patterning. Divergent gene expression between newly bifurcated sibling cell types is dominated by upregulation in the induced cell type. These upregulated genes typically include numerous transcription factors and not just one or two key regulators. The Ets family transcription factor Elk1/3/4 is upregulated in almost all the putatively direct inductions, indicating that it may act in an FGF-dependent feedback loop. We examine several bifurcations in detail and find support for a ‘broad-hourglass’ model of cell fate specification in which many genes are induced in parallel to key tissue-specific transcriptional regulators via the same set of transcriptional inputs.

scholarly journals Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu Zhang ◽  
Yueli Cui ◽  
Xinyi Ma ◽  
Jun Yong ◽  
Liying Yan ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Developmental Trajectories ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Human Pituitary ◽  
Pituitary Development ◽  
Physiological Processes ◽  
Distinct Cell ◽  
Transcriptional Landscape

Abstract The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.

scholarly journals A single-cell analysis of the molecular lineage of chordate embryogenesis

2020 ◽  
Vol 6 (45) ◽  
pp. eabc4773
Author(s):  
Tengjiao Zhang ◽  
Yichi Xu ◽  
Kaoru Imai ◽  
Teng Fei ◽  
Guilin Wang ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Lineage ◽  
Cell Types ◽  
Gene Signature ◽  
Mouse Cell ◽  
Embryonic Cell ◽  
Sequencing Analysis ◽  
Lineage Differentiation ◽  
In The Wild

Progressive unfolding of gene expression cascades underlies diverse embryonic lineage development. Here, we report a single-cell RNA sequencing analysis of the complete and invariant embryonic cell lineage of the tunicate Ciona savignyi from fertilization to the onset of gastrulation. We reconstructed a developmental landscape of 47 cell types over eight cell cycles in the wild-type embryo and identified eight fate transformations upon fibroblast growth factor (FGF) inhibition. For most FGF-dependent asymmetric cell divisions, the bipotent mother cell displays the gene signature of the default daughter fate. In convergent differentiation of the two notochord lineages, we identified additional gene pathways parallel to the master regulator T/Brachyury. Last, we showed that the defined Ciona cell types can be matched to E6.5-E8.5 stage mouse cell types and display conserved expression of limited number of transcription factors. This study provides a high-resolution single-cell dataset to understand chordate early embryogenesis and cell lineage differentiation.

scholarly journals Resolving Transcriptional States and Predicting Lineages in the Annelid Capitella teleta Using Single-Cell RNAseq

2021 ◽  
Vol 8 ◽  
Author(s):  
Abhinav Sur ◽  
Néva P. Meyer
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Neurosecretory Cells ◽  
Animal Evolution ◽  
Distinct Cell ◽  
Capitella Teleta ◽  
Unique Cell ◽  
Changes Over Time ◽  
Larval Cell

Evolution and diversification of cell types has contributed to animal evolution. However, gene regulatory mechanisms underlying cell fate acquisition during development remains largely uncharacterized in spiralians. Here we use a whole-organism, single-cell transcriptomic approach to map larval cell types in the annelid Capitella teleta at 24- and 48-h post gastrulation (stages 4 and 5). We identified eight unique cell clusters (undifferentiated precursors, ectoderm, muscle, ciliary-band, gut, neurons, neurosecretory cells, and protonephridia), thus helping to identify uncharacterized molecular signatures such as previously unknown neurosecretory cell markers in C. teleta. Analysis of coregulatory programs in individual clusters revealed gene interactions that can be used for comparisons of cell types across taxa. We examined the neural and neurosecretory clusters more deeply and characterized a differentiation trajectory starting from dividing precursors to neurons using Monocle3 and velocyto. Pseudotime analysis along this trajectory identified temporally-distinct cell states undergoing progressive gene expression changes over time. Our data revealed two potentially distinct neural differentiation trajectories including an early trajectory for brain neurosecretory cells. This work provides a valuable resource for future functional investigations to better understanding neurogenesis and the transitions from neural precursors to neurons in an annelid.

scholarly journals Single-Cell Analysis for Whole-Organism Datasets

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Angela Oliveira Pisco ◽  
Bruno Tojo ◽  
Aaron McGeever
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Data Science ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Annual Review ◽  
Publication Date ◽  
Biomedical Data ◽  
A Cell

Cell atlases are essential companions to the genome as they elucidate how genes are used in a cell type–specific manner or how the usage of genes changes over the lifetime of an organism. This review explores recent advances in whole-organism single-cell atlases, which enable understanding of cell heterogeneity and tissue and cell fate, both in health and disease. Here we provide an overview of recent efforts to build cell atlases across species and discuss the challenges that the field is currently facing. Moreover, we propose the concept of having a knowledgebase that can scale with the number of experiments and computational approaches and a new feedback loop for development and benchmarking of computational methods that includes contributions from the users. These two aspects are key for community efforts in single-cell biology that will help produce a comprehensive annotated map of cell types and states with unparalleled resolution. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 4 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Intestinal Epithelium – Fluid Fate and Rigid Structure From Crypt Bottom to Villus Tip

2021 ◽  
Vol 9 ◽  
Author(s):  
Vangelis Bonis ◽  
Carla Rossell ◽  
Helmuth Gehart
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Intestinal Epithelium ◽  
Cell Types ◽  
Stem Cell Population ◽  
Distinct Cell ◽  
Health And Disease ◽  
Spatio Temporal ◽  
Cell Fate Control ◽  
Gastro Intestinal Tract

The single-layered, simple epithelium of the gastro-intestinal tract controls nutrient uptake, coordinates our metabolism and shields us from pathogens. Despite its seemingly simple architecture, the intestinal lining consists of highly distinct cell populations that are continuously renewed by the same stem cell population. The need to maintain balanced diversity of cell types in an unceasingly regenerating tissue demands intricate mechanisms of spatial or temporal cell fate control. Recent advances in single-cell sequencing, spatio-temporal profiling and organoid technology have shed new light on the intricate micro-structure of the intestinal epithelium and on the mechanisms that maintain it. This led to the discovery of unexpected plasticity, zonation along the crypt-villus axis and new mechanism of self-organization. However, not only the epithelium, but also the underlying mesenchyme is distinctly structured. Several new studies have explored the intestinal stroma with single cell resolution and unveiled important interactions with the epithelium that are crucial for intestinal function and regeneration. In this review, we will discuss these recent findings and highlight the technologies that lead to their discovery. We will examine strengths and limitations of each approach and consider the wider impact of these results on our understanding of the intestine in health and disease.

scholarly journals Resolving transcriptional states and predicting lineages in the annelid Capitella teleta using single-cell RNAseq

2020 ◽  
Author(s):  
Abhinav Sur ◽  
Néva P. Meyer
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Neurosecretory Cells ◽  
Animal Evolution ◽  
Distinct Cell ◽  
Capitella Teleta ◽  
Unique Cell ◽  
Changes Over Time ◽  
Larval Cell

AbstractEvolution and diversification of cell types has contributed to animal evolution. However, gene regulatory mechanisms underlying cell fate acquisition during development remains largely uncharacterized in spiralians. Here we use a whole-organism, single-cell transcriptomic approach to map larval cell types in the annelid Capitella teleta at 24- and 48-hours post gastrulation (stages 4 and 5). We identified eight unique cell clusters (undifferentiated precursors, ectoderm, muscle, ciliary-band, gut, neurons, neurosecretory cells and protonephridia), thus helping to identify previously uncharacterized molecular signatures such as novel neurosecretory cell markers. Analysis of coregulatory programs in individual clusters revealed gene interactions that can be used for comparisons of cell types across taxa. We examined the neural and neurosecretory clusters more deeply and characterized a differentiation trajectory starting from dividing precursors to neurons using Monocle3 and velocyto. Pseudotime analysis along this trajectory identified temporally-distinct cell states undergoing progressive gene expression changes over time. Our data revealed two potentially distinct neural differentiation trajectories including an early trajectory for brain neurosecretory cells. This work provides a valuable resource for future functional investigations to better understanding neurogenesis and the transitions from neural precursors to neurons in an annelid.

scholarly journals A murine aging cell atlas reveals cell identity and tissue-specific trajectories of aging

2019 ◽  
Author(s):  
Jacob C. Kimmel ◽  
Lolita Penland ◽  
Nimrod D. Rubinstein ◽  
David G. Hendrickson ◽  
David R. Kelley ◽  
...  
Keyword(s):  
Single Cell ◽  
Optimal Transport ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Rna Seq ◽  
Cell Type ◽  
Distinct Cell Type ◽  
Cell Identity ◽  
Distinct Cell ◽  
Technological Limitations

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.

scholarly journals Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development

2019 ◽  
Author(s):  
Yufeng Lu ◽  
Fion Shiau ◽  
Wenyang Yi ◽  
Suying Lu ◽  
Qian Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Fate ◽  
Single Cell Analysis ◽  
Retinal Development ◽  
Cell Types ◽  
Retinal Cell ◽  
Transcriptional Networks ◽  
Species Specific

SummaryThe development of single-cell RNA-Sequencing (scRNA-Seq) has allowed high resolution analysis of cell type diversity and transcriptional networks controlling cell fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-Seq over retinal organoid and in vivo retinal development, across 20 timepoints. Using both pseudotemporal and cross-species analyses, we examined the conservation of gene expression across retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we examined gene expression differences between developing macula and periphery and between two distinct populations of horizontal cells. We also identify both shared and species-specific patterns of gene expression during human and mouse retinal development. Finally, we identify an unexpected role for ATOH7 expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development, and may help guide the design of cell-based therapies for treating retinal dystrophies.

scholarly journals Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming

2021 ◽  
Vol 22 (11) ◽  
pp. 5988
Author(s):  
Hyun Kyu Kim ◽  
Tae Won Ha ◽  
Man Ryul Lee
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Cell Fate ◽  
Human Cell ◽  
Transcriptome Analysis ◽  
Single Cell Analysis ◽  
Embryonic Stem ◽  
Single Cell Level ◽  
Cell Analysis ◽  
Cell Level

Cells are the basic units of all organisms and are involved in all vital activities, such as proliferation, differentiation, senescence, and apoptosis. A human body consists of more than 30 trillion cells generated through repeated division and differentiation from a single-cell fertilized egg in a highly organized programmatic fashion. Since the recent formation of the Human Cell Atlas consortium, establishing the Human Cell Atlas at the single-cell level has been an ongoing activity with the goal of understanding the mechanisms underlying diseases and vital cellular activities at the level of the single cell. In particular, transcriptome analysis of embryonic stem cells at the single-cell level is of great importance, as these cells are responsible for determining cell fate. Here, we review single-cell analysis techniques that have been actively used in recent years, introduce the single-cell analysis studies currently in progress in pluripotent stem cells and reprogramming, and forecast future studies.

Sign in / Sign up

Export Citation Format

Share Document