scholarly journals Microinjection of fluorescent tracers to study neural cell lineages

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 1-8
Author(s):  
Richard Wetts ◽  
Scott E. Fraser
Keyword(s):  
Molecular Level ◽  
Cell Lineage ◽  
Cell Types ◽  
Neural Retina ◽  
Restricted Range ◽  
Fluorescent Tracers ◽  
Developmental Potential ◽  
Cell Lineages ◽  
Wide Range ◽  
Single Phenotype

The examination of cell lineages is an important step towards understanding the developmental events that specify the various cell types in the organism. The mechanisms that control which cell types are formed, their locations, and their numbers remain unknown. Analyses of cell lineage in the frog neural retina have revealed that individual precursors are multipotent and are capable of producing almost any combination of cell types. In addition to giving rise to a wide range of phenotypes, the precursors can give rise to a wide range of clone sizes. Cell lineage studies in other systems indicate that some precursors are multipotent, like those in the retina, while others appear to produce a more restricted range of descendants, perhaps even a single phenotype. These differences in the developmental potential of precursor cells suggest that the nervous system uses several strategies for producing its many cell types. Investigation of these strategies, at the cellular and molecular level, requires more than a description of the normal cell lineages. We are now exploiting the frog neural retina to perform the experimental manipulations needed to elucidate these strategies.

scholarly journals A Gene Network Model for Developing Cell Lineages

2005 ◽  
Vol 11 (3) ◽  
pp. 249-267 ◽  
Author(s):  
Nicholas Geard ◽  
Janet Wiles
Keyword(s):  
Gene Network ◽  
Temporal Dynamics ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Cell Types ◽  
External Input ◽  
Sufficient Information ◽  
Cell Lineages ◽  
C Elegans ◽  
Task Definition

Biological development is a remarkably complex process. A single cell, in an appropriate environment, contains sufficient information to generate a variety of differentiated cell types, whose spatial and temporal dynamics interact to form detailed morphological patterns. While several different physical and chemical processes play an important role in the development of an organism, the locus of control is the cell's gene regulatory network. We designed a dynamic recurrent gene network (DRGN) model and evaluated its ability to control the developmental trajectories of cells during embryogenesis. Three tasks were developed to evaluate the model, inspired by cell lineage specification in C. elegans, describing the variation in gene activity required for early cell diversification, combinatorial control of cell lineages, and cell lineage termination. Three corresponding sets of simulations compared performance on the tasks for different gene network sizes, demonstrating the ability of DRGNs to perform the tasks with minimal external input. The model and task definition represent a new means of linking the fundamental properties of genetic networks with the topology of the cell lineages whose development they control.

scholarly journals Modeling lung cell development using human pluripotent stem cells

2021 ◽  
Author(s):  
Amy Wong
Keyword(s):  
Stem Cells ◽  
Lung Development ◽  
Disease Modeling ◽  
Cell Lineage ◽  
Fetal Lung ◽  
Cell Types ◽  
Cell Lineages ◽  
Lung Progenitor ◽  
Air Liquid Interface ◽  
First Time

Abstract Human PSC (hPSC) differentiations can capture developmental phenotypes and processes and are useful for studying fundamental biological mechanisms driving tissue morphogenesis and cell lineage development. Here, we show for the first time the temporal development of lung cell lineages using hPSC that model developmental milestones observed in primary tissue, the generation of renewable fetal lung epithelial spheroids, and the functional utility of the lung models at different differentiation stages for Cystic fibrosis disease modeling. We first show the presence of hPSC-derived lung progenitor cells reminiscent of early trimester lung development and containing basal stem cells that generate renewable airway spheroids. Maturation and polarization in air liquid interface (ALI) generates additional epithelial cell lineages found in adult airways including pulmonary neuroendocrine, brush, mature basal, ciliated and secretory cell types. Finally, pseudotime and RNA velocity analyses of the integrated datasets from the fetal and ALI stages reveal previously identified and new cell lineage relationships. Overall, hPSC differentiation can capture aspects of human lung development and potentially provide important insight into congenital causes of diseases.

Modifications of cell fate specification in equal-cleaving nemertean embryos: alternate patterns of spiralian development

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3175-3185 ◽  
Author(s):  
M.Q. Martindale ◽  
J.Q. Henry
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Cell Types ◽  
Embryonic Cell ◽  
Specific Cell ◽  
Cell Fate Specification ◽  
Cell Fates ◽  
Developmental Potential ◽  
Fate Specification ◽  
Symmetry Properties

The nemerteans belong to a phylum of coelomate worms that display a highly conserved pattern of cell divisions referred to as spiral cleavage. It has recently been shown that the fates of the four embryonic cell quadrants in two species of nemerteans are not homologous to those in other spiralian embryos, such as the annelids and molluscs (Henry, J. Q. and Martindale, M. Q. (1994a) Develop. Genetics 15, 64–78). Equal-cleaving molluscs utilize inductive interactions to establish quadrant-specific cell fates and embryonic symmetry properties following fifth cleavage. In order to elucidate the manner in which cell fates are established in nemertean embryos, we have conducted cell isolation and deletion experiments to examine the developmental potential of the early cleavage blastomeres of two equal-cleaving nemerteans, Nemertopsis bivittata and Cerebratulus lacteus. These two species display different modes of development: N. bivittata develops directly via a non-feeding larvae, while C. lacteus develops to form a feeding pilidium larva which undergoes a radical metamorphosis to give rise to the juvenile worm. By examining the development of certain structures and cell types characteristic of quadrant-specific fates for each of these species, we have shown that isolated blastomeres of the indirect-developing nemertean, C. lacteus, are capable of generating cell fates that are not a consequence of that cell's normal developmental program. For instance, dorsal blastomeres can form muscle fibers when cultured in isolation. In contrast, isolated blastomeres of the direct-developing species, N. bivittata do not regulate their development to the same extent. Some cell fates are specified in a precocious manner in this species, such as those that give rise to the eyes. Thus, these findings indicate that equal-cleaving spiralian embryos can utilize different mechanisms of cell fate and axis specification. The implications of these patterns of nemertean development are discussed in relation to experimental work in other spiralian embryos, and a model is presented that accounts for possible evolutionary changes in cell lineage and the process of cell fate specification amongst these protostome phyla.

scholarly journals Lineage Decision-Making within Normal Haematopoietic and Leukemic Stem Cells

2020 ◽  
Vol 21 (6) ◽  
pp. 2247
Author(s):  
Geoffrey Brown ◽  
Lucía Sánchez ◽  
Isidro Sánchez-García
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Immune Cell ◽  
Alternative Pathway ◽  
Cell Lineage ◽  
Cell Types ◽  
Haematopoietic Stem Cell ◽  
Haematopoietic Stem Cells ◽  
Wide Range ◽  
Lineage Decision

To produce the wide range of blood and immune cell types, haematopoietic stem cells can “choose” directly from the entire spectrum of blood cell fate-options. Affiliation to a single cell lineage can occur at the level of the haematopoietic stem cell and these cells are therefore a mixture of some pluripotent cells and many cells with lineage signatures. Even so, haematopoietic stem cells and their progeny that have chosen a particular fate can still “change their mind” and adopt a different developmental pathway. Many of the leukaemias arise in haematopoietic stem cells with the bulk of the often partially differentiated leukaemia cells belonging to just one cell type. We argue that the reason for this is that an oncogenic insult to the genome “hard wires” leukaemia stem cells, either through development or at some stage, to one cell lineage. Unlike normal haematopoietic stem cells, oncogene-transformed leukaemia stem cells and their progeny are unable to adopt an alternative pathway.

scholarly journals The genetics of induced pluripotency

Reproduction ◽  
2010 ◽  
Vol 139 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Amy Ralston ◽  
Janet Rossant
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Level ◽  
Embryonic Stem ◽  
Cell Types ◽  
Therapeutic Benefit ◽  
Mature Cell ◽  
Developmental Potential ◽  
Induced Pluripotency ◽  
Induced Pluripotent

The flurry of recent publications regarding reprogramming of mature cell types to induced pluripotent stem cells raises the question: what exactly is pluripotency? A functional definition is provided by examination of the developmental potential of pluripotent stem cell types. Defining pluripotency at the molecular level, however, can be a greater challenge. Here, we examine the emerging list of genes associated with induced pluripotency, with particular attention to their functional requirement in the mouse embryo. Knowledge of the requirement for these genes in the embryo and in embryonic stem cells will advance our understanding of how to reverse the developmental clock for therapeutic benefit.

scholarly journals Modeling lung cell development using human pluripotent stem cells

2021 ◽  
Author(s):  
Zoe Ngan ◽  
Henry Quach ◽  
Joshua Dierolf ◽  
Jin-A Lee ◽  
Elena Nicole Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Lung Development ◽  
Disease Modeling ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Fetal Lung ◽  
Cell Types ◽  
Cell Lineages ◽  
Lung Progenitor ◽  
Air Liquid Interface

Human PSC (hPSC) differentiations can capture developmental phenotypes and processes and are useful for studying fundamental biological mechanisms driving tissue morphogenesis and cell lineage development. Here, we show for the first time the temporal development of lung cell lineages using hPSC that model developmental milestones observed in primary tissue, the generation of renewable fetal lung epithelial organoids, and the functional utility of the lung models at different differentiation stages for Cystic fibrosis disease modeling. We first show the presence of hPSC-derived lung progenitor cells reminiscent of early trimester lung development and can capture a population enriched with basal stem cells that generates renewable airway organoids. Maturation and polarization in air liquid interface (ALI) generates additional epithelial cell lineages found in adult lung tissues including pulmonary neuroendocrine, brush, mature basal, ciliated and secretory cell types. Finally, pseudotime analysis of the integrated datasets from the fetal and ALI stages reveal the developmental trajectories of the cells as they emerge during differentiation. Overall, hPSC differentiation can capture aspects of human lung development and potentially provide important insight into congenital causes of diseases.

Transcriptional activity of MEF2 during mouse embryogenesis monitored with a MEF2-dependent transgene

Development ◽  
1999 ◽  
Vol 126 (10) ◽  
pp. 2045-2052 ◽  
Author(s):  
F.J. Naya ◽  
C. Wu ◽  
J.A. Richardson ◽  
P. Overbeek ◽  
E.N. Olson
Keyword(s):  
Dna Sequences ◽  
Transcriptional Activity ◽  
Cell Types ◽  
Neural Cell ◽  
Adult Brain ◽  
Mouse Embryogenesis ◽  
Cell Lineages ◽  
Nonmuscle Cell ◽  
Wide Range ◽  
Flanking Sequences

The four members of the MEF2 family of MADS-box transcription factors, MEF2-A, MEF2-B, MEF2-C and MEF2-D, are expressed in overlapping patterns in developing muscle and neural cell lineages during embryogenesis. However, during late fetal development and postnatally, MEF2 transcripts are also expressed in a wide range of cell types. Because MEF2 expression is controlled by translational and post-translational mechanisms, it has been unclear whether the presence of MEF2 transcripts in the embryo reflects transcriptionally active MEF2 proteins. To define the temporospatial expression pattern of transcriptionally active MEF2 proteins during mouse embryogenesis, we generated transgenic mice harboring a lacZ reporter gene controlled by three tandem copies of the MEF2 site and flanking sequences from the desmin enhancer, which is active in cardiac, skeletal and smooth muscle cells. Expression of this MEF2-dependent transgene paralleled expression of MEF2 mRNAs in developing myogenic lineages and regions of the adult brain. However, it was not expressed in other cell types that express MEF2 transcripts. Tandem copies of the MEF2 site from the c-jun promoter directed expression in a similar pattern to the desmin MEF2 site, suggesting that transgene expression reflects the presence of transcriptionally active MEF2 proteins, rather than other factors specific for DNA sequences flanking the MEF2 site. These results demonstrate the presence of transcriptionally active MEF2 proteins in the early muscle and neural cell lineages during embryogenesis and argue against the existence of lineage-restricted MEF2 cofactors that discriminate between MEF2 sites with different immediate flanking sequences. The discordance between MEF2 mRNA expression and MEF2 transcriptional activity in nonmuscle cell types of embryos and adults also supports the notion that post-transcriptional mechanisms regulate the expression of MEF2 proteins.

The role of cell lineage in development

1985 ◽  
Vol 312 (1153) ◽  
pp. 3-19 ◽  
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Early Embryo ◽  
Embryonic Cell ◽  
Evolutionary Divergence ◽  
Causative Role ◽  
Embryonic Cells ◽  
Developmental Potential ◽  
Cell Lineages

Studies of the role of cell lineage in development began in the latter part of the 19th century, fell into decline in the early part of the 20th, and were revived about 20 years ago. This recent revival was accompanied by the introduction of new and powerful analytical techniques. Concepts of importance for cell lineage studies include the principal division modes by which a cell may give rise to its descendant clone (proliferative, stem cell and diversifying); developmental determinacy , or indeterminacy , which refer to the degree to which the normal cleavage pattern of the early embryo and the developmental fate of its individual cells is, or is not, the same in specimen after specimen; commitment , which refers to the restriction of the developmental potential of a pluripotent embryonic cell; and equivalence group , which refers to two or more equivalently pluripotent cell clones that normally take on different fates but of which under abnormal conditions one clone can take on the fate of another. Cell lineage can be inferred to have a causative role in developmental cell fate in embryos in which induced changes in cell division patterns lead to changes in cell fate. Moreover, such a causative role of cell lineage is suggested by cases where homologous cell types characteristic of a symmetrical and longitudinally metameric body plan arise via homologous cell lineages. The developmental pathways of commitment to particular cell fates proceed according to a mixed typologic and topographic hierarchy, which appears to reflect an evolutionary compromise between maximizing the ease of ordering the spatial distribution of the determinants of commitment and minimizing the need for migration of differentially committed embryonic cells. Comparison of the developmental cell lineages in leeches and insects indicates that the early course of embryogenesis is radically different in these phyletically related taxa. This evolutionary divergence of the course of early embryogenesis appears to be attributable to an increasing prevalence of polyclonal rather than monoclonal commitment in the phylogenetic line leading from an annelid-like ancestor to insects.

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 Generation of human blastocyst-like structures from pluripotent stem cells

2021 ◽  
Author(s):  
Yong Fan ◽  
Zhe-Ying Min ◽  
Samhan Alsolami ◽  
Zheng-Lai Ma ◽  
Ke Zhong ◽  
...  
Keyword(s):  
Single Cell ◽  
Developmental Stages ◽  
Three Dimensional ◽  
Cell Lineage ◽  
Human Embryos ◽  
Developmental Potential ◽  
Cell Lineages ◽  
Human Embryogenesis ◽  
Post Implantation

AbstractHuman blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast, and primitive endoderm, all of which are essential for early development and organ formation1,2. However, due to ethical concerns and restricted access to human blastocysts, we lack a comprehensive understanding of early human embryogenesis. To bridge this knowledge gap, we need a reliable model system that recapitulates early stages of human embryogenesis. Here we report a ∼three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids also exhibited the developmental potential to undergo post-implantation morphogenesis in vitro to form structures with a cellular composition and transcriptome signature similar to human embryos that had been cultured in vitro for 8 or 10 days. In conclusion, human EPS-blastoids provide a new experimental platform for studying early developmental stages of the human embryo.HighlightsA method for generating human blastoids from EPS cells.Human blastoids resemble blastocysts in terms of morphology and cell lineage composition.Single-cell transcriptomic analyses reveal EPI, PE, and TE cell lineages in human blastoids.Human blastoids mimic in vitro the morphogenetic events of pre- and early post-implantation stages.

Sign in / Sign up

Export Citation Format

Share Document