Cell movements and cell fate during zebrafish gastrulation

Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 65-73 ◽  
Author(s):  
Robert K. Ho
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Fate Map ◽  
Cell Fates ◽  
Cell Lineages ◽  
Cell Position ◽  
Vertebrate Embryo ◽  
Cellular Identity ◽  
Transplantation Experiments

The early lineages of the zebrafish are indeterminate and a single cell labeled before the late blastula period will contribute progeny to a variety of tissues. Therefore, early cell lineages in the zebrafish do not establish future cell fates and early blastomeres must necessarily remain pluripotent. Eventually, after a period of random cell mixing, individual cells do become tissue restricted according to their later position within the blastoderm. The elucidation of a fate map for the zebrafish gastrula (Kimmel et al., 1990), has made it possible to study the processes by which cellular identity is conferred and maintained in the zebrafish. In this chapter, I describe single cell transplantation experiments designed to test for the irreversible restriction or ‘commitment’ of embryonic blastomeres in the zebrafish embryo. These experiments support the hypothesis that cell fate in the vertebrate embryo is determined by cell position. Work on the spadetail mutation will also be reviewed; this mutation causes a subset of mesodermal precursors to mismigrate during gastrulation thereby leading to a change in their eventual cell identity.

scholarly journals Single cell RNA-seq identifies developing corneal cell fates in the human cornea organoid

2021 ◽  
Author(s):  
George Maiti ◽  
Maithe Rocha Monteiro de Barros ◽  
Nan Hu ◽  
Mona Roshan ◽  
Karl J Wahlin ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Three Dimensional ◽  
Cell Types ◽  
Human Cornea ◽  
Equal Proportion ◽  
Fate Map ◽  
Cell Fates ◽  
Developmental States ◽  
Induced Pluripotent

The cornea is a protective and refractive barrier in the eye crucial for vision. Understanding the human cornea in health, disease and cell-based treatments can be greatly advanced with cornea organoids developed in culture from induced pluripotent stem cells. While a limited number of studies have investigated the single-cell transcriptomic composition of the human cornea, its organoids have not been examined similarly. Here we elucidated the transcriptomic cell fate map of 4 month-old human cornea organoids and the central cornea from three donors. The organoids harbor cell clusters representing corneal epithelium, stroma and endothelium with sub populations that capture signatures of early developmental states. Unlike the adult cornea where the largest cell population is stromal, the organoids develop almost equal proportion of the three major cell types. These corneal organoids offer a three-dimensional platform to model corneal diseases and integrated responses of the different cell types to treatments.

scholarly journals Duplication of spiralian-specific TALE genes and evolution of the blastomere specification mechanism in the bivalve lineage

EvoDevo ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Supanat Phuangphong ◽  
Jumpei Tsunoda ◽  
Hiroshi Wada ◽  
Yoshiaki Morino
Keyword(s):  
Cell Fate ◽  
Early Development ◽  
Expression Patterns ◽  
Cell Fate Specification ◽  
Fate Map ◽  
Cell Fates ◽  
Cell Specification ◽  
Cytoplasmic Content ◽  
Gene Regulatory ◽  
Unique Cell

Abstract Background Despite the conserved pattern of the cell-fate map among spiralians, bivalves display several modified characteristics during their early development, including early specification of the D blastomere by the cytoplasmic content, as well as the distinctive fate of the 2d blastomere. However, it is unclear what changes in gene regulatory mechanisms led to such changes in cell specification patterns. Spiralian-TALE (SPILE) genes are a group of spiralian-specific transcription factors that play a role in specifying blastomere cell fates during early development in limpets. We hypothesised that the expansion of SPILE gene repertoires influenced the evolution of the specification pattern of blastomere cell fates. Results We performed a transcriptome analysis of early development in the purplish bifurcate mussel and identified 13 SPILE genes. Phylogenetic analysis of the SPILE gene in molluscs suggested that duplications of SPILE genes occurred in the bivalve lineage. We examined the expression patterns of the SPILE gene in mussels and found that some SPILE genes were expressed in quartet-specific patterns, as observed in limpets. Furthermore, we found that several SPILE genes that had undergone gene duplication were specifically expressed in the D quadrant, C and D quadrants or the 2d blastomere. These expression patterns were distinct from the expression patterns of SPILE in their limpet counterparts. Conclusions These results suggest that, in addition to their ancestral role in quartet specification, certain SPILE genes in mussels contribute to the specification of the C and D quadrants. We suggest that the expansion of SPILE genes in the bivalve lineage contributed to the evolution of a unique cell fate specification pattern in bivalves.

scholarly journals Hidden heterogeneity and circadian-controlled cell fate inferred from single cell lineages

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Shaon Chakrabarti ◽  
Andrew L. Paek ◽  
Jose Reyes ◽  
Kathleen A. Lasick ◽  
Galit Lahav ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Lineages

scholarly journals A single-cell–resolution fate map of endoderm reveals demarcation of pancreatic progenitors by cell cycle

2021 ◽  
Vol 118 (25) ◽  
pp. e2025793118
Author(s):  
Yun Yang ◽  
Hao Wang ◽  
Jia He ◽  
Wenchao Shi ◽  
Zhanmei Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Developmental Trajectories ◽  
Cell Labeling ◽  
G1 Phase ◽  
Fate Map ◽  
Pancreatic Progenitor ◽  
Foregut Endoderm

A progenitor cell could generate a certain type or multiple types of descendant cells during embryonic development. To make all the descendant cell types and developmental trajectories of every single progenitor cell clear remains an ultimate goal in developmental biology. Characterizations of descendant cells produced by each uncommitted progenitor for a full germ layer represent a big step toward the goal. Here, we focus on early foregut endoderm, which generates foregut digestive organs, including the pancreas, liver, foregut, and ductal system, through distinct lineages. Using unbiased single-cell labeling techniques, we label every individual zebrafish foregut endodermal progenitor cell out of 216 cells to visibly trace the distribution and number of their descendant cells. Hence, single-cell–resolution fate and proliferation maps of early foregut endoderm are established, in which progenitor regions of each foregut digestive organ are precisely demarcated. The maps indicate that the pancreatic endocrine progenitors are featured by a cell cycle state with a long G1 phase. Manipulating durations of the G1 phase modulates pancreatic progenitor populations. This study illustrates foregut endodermal progenitor cell fate at single-cell resolution, precisely demarcates different progenitor populations, and sheds light on mechanistic insights into pancreatic fate determination.

scholarly journals Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes

2019 ◽  
Author(s):  
Nadia S. Kurd ◽  
Ashley Hoover ◽  
Jaewon Yoon ◽  
Brian M. Weist ◽  
Ellen A. Robey
Keyword(s):  
T Cell ◽  
Cell Fate ◽  
Negative Selection ◽  
Intraepithelial Lymphocytes ◽  
Cell Fates ◽  
Thymic Tissue ◽  
Migration Patterns ◽  
Cell Lineages ◽  
The Impact ◽  
Selection Of

ABSTRACTThymocytes bearing αβ T cell receptors (TCRαβ) with high affinity for self-peptide-MHC complexes undergo negative selection or are diverted to alternate T cell lineages, a process termed agonist selection. Among thymocytes bearing TCRs restricted to MHC class I, agonist selection can lead to the development of precursors that can home to the gut and give rise to CD8αα-expressing intraepithelial lymphocytes (CD8αα IELs). The factors that influence the choice between negative selection versus CD8αα IEL development remain largely unknown. Using a synchronized thymic tissue slice model that supports both negative selection and CD8αα̣IEL development, we show that the affinity threshold for CD8αα IEL development is higher than for negative selection. We also investigate the impact of peptide presenting cells and cytokines, and the migration patterns associated with these alternative cell fates. Our data highlight the roles of TCR affinity and the thymic microenvironments on T cell fate.

scholarly journals Single cell tracing reveals heterogeneous drug-, dose-, and time-dependent effects on cancer cell fates

2020 ◽  
Author(s):  
Sean M. Gross ◽  
Crystal Sanchez-Aguila ◽  
Paulina J. Zhan ◽  
Laura M. Heiser
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Cancer Cells ◽  
Cell Fate ◽  
Drug Dose ◽  
Time Dependent ◽  
Cell Fates ◽  
Drug Induced ◽  
Induced Apoptosis ◽  
Induced Changes

ABSTRACTUnderstanding the molecular basis for drug-induced changes in cellular responses is critical for the identification of effective cancer treatments. Measurement of endpoint viability across a range of drug doses is the standard approach to quantify drug efficacy. While informative, this read-out does not account for the multiple cell fate decisions individual cancer cells undergo in response to drug treatment. As a consequence, the basis for drug-induced changes in cell numbers remains poorly defined. To evaluate the impact of cancer drugs on individual cells, we engineered AU565 breast cancer cells to express a fluorescent cell cycle reporter and then assessed dynamic responses to a panel of drugs. Detailed population and single cell analyses revealed heterogeneous drug-, dose-, and time-dependent effects on cell cycle durations and cell fates. Lapatinib induced dose-dependent extension of G1 duration and limited apoptosis. In contrast, cell fate responses varied with gemcitabine dose: low gemcitabine doses induced extension of S-G2 durations, whereas high doses induced apoptosis after prolonged exposure. Lastly, paclitaxel induced apoptosis and caused only modest cell cycle effects. Overall, our analyses revealed that each drug induced distinct impacts on cell fate that were dependent on the dose and duration of treatment. Understanding these differences has implications for the mechanisms of therapeutic resistance and the identification of effective drug combinations and treatment schedules.

scholarly journals Epigenetic regulation of hematopoiesis by DNA methylation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Aniket V Gore ◽  
Brett Athans ◽  
James R Iben ◽  
Kristin Johnson ◽  
Valya Russanova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Dna Methyltransferase ◽  
Epigenetic Mechanism ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Cell Type Specific ◽  
Cellular Identity

During embryonic development, cell type-specific transcription factors promote cell identities, while epigenetic modifications are thought to contribute to maintain these cell fates. Our understanding of how genetic and epigenetic modes of regulation work together to establish and maintain cellular identity is still limited, however. Here, we show that DNA methyltransferase 3bb.1 (dnmt3bb.1) is essential for maintenance of hematopoietic stem and progenitor cell (HSPC) fate as part of an early Notch-runx1-cmyb HSPC specification pathway in the zebrafish. Dnmt3bb.1 is expressed in HSPC downstream from Notch1 and runx1, and loss of Dnmt3bb.1 activity leads to reduced cmyb locus methylation, reduced cmyb expression, and gradual reduction in HSPCs. Ectopic overexpression of dnmt3bb.1 in non-hematopoietic cells is sufficient to methylate the cmyb locus, promote cmyb expression, and promote hematopoietic development. Our results reveal an epigenetic mechanism supporting the maintenance of hematopoietic cell fate via DNA methylation-mediated perdurance of a key transcription factor in HSPCs.

scholarly journals Single-cell transcriptomics of the mouse gonadal soma reveals the establishment of sexual dimorphism in distinct cell lineages

2018 ◽  
Author(s):  
Isabelle Stévant ◽  
Françoise Kühne ◽  
Andy Greenfield ◽  
Marie-Christine Chaboissier ◽  
Emmanouil T. Dermitzakis ◽  
...  
Keyword(s):  
Time Series ◽  
Sex Determination ◽  
Single Cell ◽  
Cell Fate ◽  
Somatic Cells ◽  
Supporting Cells ◽  
Single Population ◽  
Cell Lineages ◽  
Multipotent Progenitors ◽  
Distinct Cell

SummarySex determination is a unique process that allows the study of multipotent progenitors and their acquisition of sex-specific fates during differentiation of the gonad into a testis or an ovary. Using time-series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP+ somatic cells during sex determination, we identified a single population of early progenitors giving rise to both pre-granulosa cells and potential steroidogenic precursor cells. By comparing time-series scRNA-seq of XX and XY somatic cells, we demonstrate that the supporting cells emerge from the early progenitors with a non-sex-specific transcriptomic program, before pre-granulosa and Sertoli cells acquire their sex-specific identity. In XX and XY steroidogenic precursors similar transcriptomic profiles underlie the acquisition of cell fate, but with a delay in XX cells. Our data provide a novel framework, at single-cell resolution, for further interrogation of the molecular and cellular basis of mammalian sex determination.

scholarly journals Duplication of Spiralian-Specific TALE Genes And Evolution of The Blastomere Specification Mechanism In The Bivalve Lineage

2021 ◽  
Author(s):  
Supanat Phuangphong ◽  
Jumpei Tsunoda ◽  
Hiroshi Wada ◽  
Yoshiaki Morino
Keyword(s):  
Cell Fate ◽  
Early Development ◽  
Functional Divergence ◽  
Expression Patterns ◽  
Fate Map ◽  
Cell Fates ◽  
Cell Specification ◽  
Cytoplasmic Content ◽  
Gene Regulatory ◽  
Unique Cell

Abstract Background Despite the conserved pattern of the cell-fate map among spiralians, bivalves display several modified characteristics during their early development, including early specification of the D blastomere by the cytoplasmic content, as well as the distinctive fate of the 2d blastomere. However, it is unclear what changes in gene regulatory mechanisms led to such changes in cell specification patterns. Spiralian-TALE (SPILE) genes are a group of spiralian-specific transcription factors that play a role in specifying blastomere cell fates during early development in limpets. We hypothesised that the expansion of SPILE gene repertoires influenced the evolution of the specification pattern of blastomere cell fates.Results We performed a transcriptome analysis of early development in the purplish bifurcate mussel and identified 13 SPILE genes. Phylogenetic analysis of the SPILE gene in bivalves and limpets suggested that extra duplications of SPILE genes occurred in the bivalve lineage. We examined the expression patterns of the SPILE gene in mussels and found that some SPILE genes were expressed in quartet-specific patterns, as observed in limpets. Furthermore, we found that several SPILE genes that had undergone gene duplication were specifically expressed in the D quadrant, C and D quadrants or the 2d blastomere. These expression patterns were distinct from the expression patterns of SPILE in their limpet counterparts. Conclusions These results suggest that, in addition to their ancestral role in quartet specification, bivalve SPILE genes contributed to the specification of C and D quadrants. We propose that the expansion of SPILE genes in the bivalve lineage created extra SPILE genes that underwent expression pattern and functional divergence, thereby resulting in the evolution of a unique cell-fate specification pattern in bivalves.

scholarly journals FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data

2017 ◽  
Author(s):  
J.S. Herman ◽  
Sagar ◽  
D. Grün
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Learning Algorithm ◽  
Cell Fates ◽  
Lineage Differentiation ◽  
Multipotent Progenitors ◽  
Distinct Cell ◽  
Distinct Lineage ◽  
Cell Transcriptome

Differentiation of multipotent cells is a complex process governed by interactions of thousands of genes subject to substantial expression fluctuations. Resolving cell state heterogeneity arising during this process requires quantification of gene expression within individual cells. However, computational methods linking this heterogeneity to biases towards distinct cell fates are not well established. Here, we perform deep single-cell transcriptome sequencing of ~2,000 bone-marrow derived mouse hematopoietic progenitors enriched for lymphoid lineages. To resolve subtle transcriptome priming indicative of distinct lineage biases, we developed FateID, an iterative supervised learning algorithm for the probabilistic quantification of cell fate bias. FateID delineates domains of fate bias within progenitor populations and permits the derivation of high-resolution differentiation trajectories, revealing a common progenitor population of B cells and plasmacytoid dendritic cells, which we validated by in vitro differentiation assays. We expect that FateID will enhance our understanding of the process of cell fate choice in complex multi-lineage differentiation systems.

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