scholarly journals Clonal analysis and dynamic imaging identify multipotency of individual Gallus gallus caudal hindbrain neural crest cells toward cardiac and enteric fates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weiyi Tang ◽  
Yuwei Li ◽  
Ang Li ◽  
Marianne E. Bronner
Keyword(s):  
Neural Crest ◽  
Single Cell ◽  
Cell Fate ◽  
Neural Crest Cells ◽  
Time Lapse ◽  
Cell Types ◽  
Clonal Analysis ◽  
Dynamic Imaging ◽  
Lineage Tracing ◽  
Enteric Ganglia

AbstractNeural crest stem cells arising from caudal hindbrain (often called cardiac and posterior vagal neural crest) migrate long distances to form cell types as diverse as heart muscle and enteric ganglia, abnormalities of which lead to common congenital birth defects. Here, we explore whether individual caudal hindbrain neural crest precursors are multipotent or predetermined toward these particular fates and destinations. To this end, we perform lineage tracing of chick neural crest cells at single-cell resolution using two complementary approaches: retrovirally mediated multiplex clonal analysis and single-cell photoconversion. Both methods show that the majority of these neural crest precursors are multipotent with many clones producing mesenchymal as well as neuronal derivatives. Time-lapse imaging demonstrates that sister cells can migrate in distinct directions, suggesting stochasticity in choice of migration path. Perturbation experiments further identify guidance cues acting on cells in the pharyngeal junction that can influence this choice; loss ofCXCR4signaling results in failure to migrate to the heart but no influence on migration toward the foregut, whereas loss ofRETsignaling does the opposite. Taken together, the results suggest that environmental influences rather than intrinsic information govern cell fate choice of multipotent caudal hindbrain neural crest cells.

scholarly journals Cyclic AMP Signaling Functions as a Bimodal Switch in Sympathoadrenal Cell Development in Cultured Primary Neural Crest Cells

2000 ◽  
Vol 20 (9) ◽  
pp. 3004-3014 ◽  
Author(s):  
Matthew L. Bilodeau ◽  
Theresa Boulineau ◽  
Ronald L. Hullinger ◽  
Ourania M. Andrisani
Keyword(s):  
Cyclic Amp ◽  
Neural Crest ◽  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Cell Development ◽  
Camp Signaling ◽  
Camp Signaling Pathway ◽  
Trunk Neural Crest

ABSTRACT Cells of the vertebrate neural crest (crest cells) are an invaluable model system to address cell fate specification. Crest cells are amenable to tissue culture, and they differentiate to a variety of neuronal and nonneuronal cell types. Earlier studies have determined that bone morphogenetic proteins (BMP-2, -4, and -7) and agents that elevate intracellular cyclic AMP (cAMP) stimulate the development of the sympathoadrenal (SA, adrenergic) lineage in neural crest cultures. To investigate whether interactive mechanisms between signaling pathways influence crest cell differentiation, we characterized the combinatorial effects of BMP-2 and cAMP-elevating agents on the development of quail trunk neural crest cells in primary culture. We report that the cAMP signaling pathway modulates both positive and negative signals influencing the development of SA cells. Specifically, we show that moderate activation of cAMP signaling promotes, in synergy with BMP-2, SA cell development and the expression of the SA lineage-determining gene Phox2a. By contrast, robust activation of cAMP signaling opposes, even in the presence of BMP-2, SA cell development and the expression of the SA lineage-determining ASH-1 and Phox2 genes. We conclude that cAMP signaling acts as a bimodal regulator of SA cell development in neural crest cultures.

The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4127-4138 ◽  
Author(s):  
Mirella Dottori ◽  
Michael K. Gross ◽  
Patricia Labosky ◽  
Martyn Goulding
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Winged Helix ◽  
Multiple Cell ◽  
Winged Helix Transcription Factor

The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.

scholarly journals Neural crest lineage analysis: from past to future trajectory

Development ◽  
2020 ◽  
Vol 147 (20) ◽  
pp. dev193193 ◽  
Author(s):  
Weiyi Tang ◽  
Marianne E. Bronner
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Single Molecule ◽  
Cell Lineage ◽  
Neural Crest Cell ◽  
Cell Types ◽  
Lineage Tracing ◽  
Migration Routes ◽  
Developmental Potential ◽  
Lineage Analysis

ABSTRACTSince its discovery 150 years ago, the neural crest has intrigued investigators owing to its remarkable developmental potential and extensive migratory ability. Cell lineage analysis has been an essential tool for exploring neural crest cell fate and migration routes. By marking progenitor cells, one can observe their subsequent locations and the cell types into which they differentiate. Here, we review major discoveries in neural crest lineage tracing from a historical perspective. We discuss how advancing technologies have refined lineage-tracing studies, and how clonal analysis can be applied to questions regarding multipotency. We also highlight how effective progenitor cell tracing, when combined with recently developed molecular and imaging tools, such as single-cell transcriptomics, single-molecule fluorescence in situ hybridization and high-resolution imaging, can extend the scope of neural crest lineage studies beyond development to regeneration and cancer initiation.

scholarly journals Single cell RNA analysis of trunk neural crest cells in zebrafish identifies pre-migratory populations expressing markers of differentiated derivatives

2020 ◽  
Author(s):  
Ezra Lencer ◽  
Rytis Prekeris ◽  
Kristin Bruk Artinger
Keyword(s):  
Neural Crest ◽  
Single Cell ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Vertebrate Development ◽  
Multiple Traits ◽  
Transcriptional Changes ◽  
Trunk Neural Crest ◽  
Crest Cell

AbstractThe neural crest is a migratory population of stem-like cells that contribute to multiple traits including the bones of the skull, peripheral nervous system, and pigment. How neural crest cells differentiate into diverse cell types is a fundamental question in the study of vertebrate biology. Here, we use single cell RNA sequencing to characterize transcriptional changes associated with neural crest cell development in the zebrafish trunk during the early stages of migration. We show that neural crest cells are transcriptionally diverse, and identify pre-migratory populations already expressing genes associated with differentiated derivatives. Further, we identify a population of Rohon-Beard neurons that are shown to be sources of Fgf signaling in the zebrafish trunk. The data presented identify novel genetic markers for multiple trunk neural crest cell populations and Rohon-Beard neurons providing insight into previously uncharacterized genes critical for vertebrate development.

scholarly journals Spatiotemporal structure of cell fate decisions in murine neural crest

Science ◽  
2019 ◽  
Vol 364 (6444) ◽  
pp. eaas9536 ◽  
Author(s):  
Ruslan Soldatov ◽  
Marketa Kaucka ◽  
Maria Eleni Kastriti ◽  
Julian Petersen ◽  
Tatiana Chontorotzea ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Single Cell Analysis ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Phenotypic Traits ◽  
Cell Fate Decisions ◽  
Numerous Cell ◽  
Trunk Neural Crest ◽  
Cranial Neural Crest Cells

Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single-cell analysis, we show that mouse trunk neural crest cells become biased toward neuronal lineages when they delaminate from the neural tube, whereas cranial neural crest cells acquire ectomesenchyme potential dependent on activation of the transcription factor Twist1. The choices that neural crest cells make to become sensory, glial, autonomic, or mesenchymal cells can be formalized as a series of sequential binary decisions. Each branch of the decision tree involves initial coactivation of bipotential properties followed by gradual shifts toward commitment. Competing fate programs are coactivated before cells acquire fate-specific phenotypic traits. Determination of a specific fate is achieved by increased synchronization of relevant programs and concurrent repression of competing fate programs.

scholarly journals Lineage recording of zebrafish embryogenesis reveals historical and ongoing lineage commitments

2020 ◽  
Author(s):  
Zhuoxin Chen ◽  
Chang Ye ◽  
Zhan Liu ◽  
Shanjun Deng ◽  
Xionglei He ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Lineage ◽  
Cell Types ◽  
Lineage Tracing ◽  
Cell Type ◽  
Single Cell Sequencing ◽  
Sequencing Technologies ◽  
Development And Differentiation ◽  
Zebrafish Embryogenesis

AbstractIt has been challenging to characterize the lineage relationships among cells in vertebrates, which comprise a great number of cells. Fortunately, recent progress has been made by combining the CRISPR barcoding system with single-cell sequencing technologies to provide an unprecedented opportunity to track lineage at single-cell resolution. However, due to errors and/or dropouts introduced by amplification and sequencing, reconstruction of accurate lineage relationships in complex organisms remains a challenge. Thus, improvements in both experimental design and computational analysis are necessary for lineage inference. In this study, we employed single-cell Lineage tracing On Endogenous Scarring Sites (scLOESS), a lineage recording strategy based on the CRISPR-Cas9 system, to trace cell fate commitments for zebrafish larvae. With rigorous quality control, we demonstrated that lineage commitments of complex organisms could be inferred from a limited number of barcoding sites. Together with cell-type characterization, our method could homogenously recover lineage information. In combination with the cell-type and lineage information, we depicted the development histories for germ layers as well as cell types. Furthermore, when combined with trajectory analysis, our methods could capture and resolve the ongoing lineage commitment events to gain further biological insights into later development and differentiation in complex organisms.

scholarly journals Lineage analysis reveals an endodermal contribution to the vertebrate pituitary

Science ◽  
2020 ◽  
Vol 370 (6515) ◽  
pp. 463-467 ◽  
Author(s):  
Peter Fabian ◽  
Kuo-Chang Tseng ◽  
Joanna Smeeton ◽  
Joseph J. Lancman ◽  
P. Duc Si Dong ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Endocrine Cell ◽  
Time Lapse ◽  
Cell Types ◽  
Lineage Tracing ◽  
Single Cell Rna Sequencing ◽  
Growth Metabolism ◽  
Time Lapse Imaging ◽  
Lineage Analysis

Vertebrate sensory organs arise from epithelial thickenings called placodes. Along with neural crest cells, cranial placodes are considered ectodermal novelties that drove evolution of the vertebrate head. The anterior-most placode generates the endocrine lobe [adenohypophysis (ADH)] of the pituitary, a master gland controlling growth, metabolism, and reproduction. In addition to known ectodermal contributions, we use lineage tracing and time-lapse imaging in zebrafish to identify an endodermal contribution to the ADH. Single-cell RNA sequencing of the adult pituitary reveals similar competency of endodermal and ectodermal epithelia to generate all endocrine cell types. Further, endoderm can generate a rudimentary ADH-like structure in the near absence of ectodermal contributions. The fish condition supports the vertebrate pituitary arising through interactions of an ancestral endoderm-derived proto-pituitary with newly evolved placodal ectoderm.

scholarly journals Single-cell RNA analysis identifies pre-migratory neural crest cells expressing markers of differentiated derivatives

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ezra Lencer ◽  
Rytis Prekeris ◽  
Kristin Bruk Artinger
Keyword(s):  
Neural Crest ◽  
Single Cell ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Vertebrate Development ◽  
Multiple Traits ◽  
Transcriptional Changes ◽  
Trunk Neural Crest ◽  
Crest Cell

The neural crest is a migratory population of stem-like cells that contribute to multiple traits including the bones of the skull, peripheral nervous system, and pigment. How neural crest cells differentiate into diverse cell types is a fundamental question in the study of vertebrate biology. Here, we use single-cell RNA sequencing to characterize transcriptional changes associated with neural crest cell development in the zebrafish trunk during the early stages of migration. We show that neural crest cells are transcriptionally diverse and identify pre-migratory populations already expressing genes associated with differentiated derivatives, specifically in the xanthophore lineage. Further, we identify a population of Rohon–Beard neurons in the data. The data presented identify novel genetic markers for multiple trunk neural crest cell populations and Rohon–Beard neurons providing insight into previously uncharacterized genes critical for vertebrate development.

scholarly journals Taking a Step Back: Insights into the Mechanisms Regulating Gut Epithelial Dedifferentiation

2021 ◽  
Vol 22 (13) ◽  
pp. 7043
Author(s):  
Shaida Ouladan ◽  
Alex Gregorieff
Keyword(s):  
Cell Fate ◽  
Hormonal Regulation ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
Physical Damage ◽  
Epithelial Regeneration ◽  
Gut Epithelium ◽  
Stem Cell Populations

Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades. Increasingly, however, researchers are turning their attention to unraveling the mechanisms driving gut epithelial regeneration due to physical damage or infection. It is now well established that injury to the gut barrier triggers major cell fate changes, demonstrating the highly plastic nature of the gut epithelium. In particular, lineage tracing and transcriptional profiling experiments have uncovered several injury-induced stem-cell populations and molecular markers of the regenerative state. Despite the progress achieved in recent years, several questions remain unresolved, particularly regarding the mechanisms driving dedifferentiation of the gut epithelium. In this review, we summarize the latest studies, primarily from murine models, that define the regenerative processes governing the gut epithelium and discuss areas that will require more in-depth investigation.

scholarly journals Generative modeling of single-cell population time series for inferring cell differentiation landscapes

2020 ◽  
Author(s):  
Grace H.T. Yeo ◽  
Sachit D. Saksena ◽  
David K. Gifford
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Lineage Tracing ◽  
Model Framework ◽  
Modeling Framework ◽  
Generative Modeling ◽  
Model Complex

SummaryExisting computational methods that use single-cell RNA-sequencing for cell fate prediction either summarize observations of cell states and their couplings without modeling the underlying differentiation process, or are limited in their capacity to model complex differentiation landscapes. Thus, contemporary methods cannot predict how cells evolve stochastically and in physical time from an arbitrary starting expression state, nor can they model the cell fate consequences of gene expression perturbations. We introduce PRESCIENT (Potential eneRgy undErlying Single Cell gradIENTs), a generative modeling framework that learns an underlying differentiation landscape from single-cell time-series gene expression data. Our generative model framework provides insight into the process of differentiation and can simulate differentiation trajectories for arbitrary gene expression progenitor states. We validate our method on a recently published experimental lineage tracing dataset that provides observed trajectories. We show that this model is able to predict the fate biases of progenitor cells in neutrophil/macrophage lineages when accounting for cell proliferation, improving upon the best-performing existing method. We also show how a model can predict trajectories for cells not found in the model’s training set, including cells in which genes or sets of genes have been perturbed. PRESCIENT is able to accommodate complex perturbations of multiple genes, at different time points and from different starting cell populations. PRESCIENT models are able to recover the expected effects of known modulators of cell fate in hematopoiesis and pancreatic β cell differentiation.

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