scholarly journals Modeling the bistable transition between cell phenotypes during limb precartilage condensation

2021 ◽  
Author(s):  
Tilmann Glimm ◽  
Bogdan Kazmierczak ◽  
Cheng Cui ◽  
Stuart A Newman ◽  
Ramray Bhat
Keyword(s):  
Reaction Network ◽  
Reaction Diffusion ◽  
Mesenchymal Cell ◽  
Cell Types ◽  
Limb Bud ◽  
Bistable Switch ◽  
Embryonic Limb ◽  
Cell Phenotypes ◽  
And Diffusion ◽  
Very High

Previous work showed that Gal-8 and Gal-1A, two proteins belonging to the galactoside-binding galectin family, are the earliest determinants of the patterning of the skeletal elements of embryonic chicken limbs, and further, that their experimentally determined interactions in the embryonic limb bud can be interpreted through a reaction-diffusion-adhesion framework. Here, we use an ordinary differential equation-based approach to analyze the intrinsic switching modality of the galectin reaction network and characterize the states of the network independent of the diffusive and adhesive arms of the patterning mechanism. We identify two steady states: where the concentrations of both the galectins are respectively, negligible, and very high. We provide an explicit Lyapunov function, which shows that there are no periodic solutions. In an extension of the model with sigmoidal galectin production terms, we show that an analogous bistable switch-like system arises via saddle-node bifurcation from a monostable one. Our model therefore predicts that the galectin network may exist in low expression and high expression states separated in space or time without any intermediate states. We verify these predictions in experiments performed with high density micromass cultures of chick limb mesenchymal cells and observe that cells inside and outside the precartilage protocondensations exhibit distinct behaviors with respect to galectin expression, motility, and spreading behavior on their substratum. The interactional complexity of the Gal-1 and -8-based patterning network is therefore sufficient to partition the mesenchymal cell population into two discrete cell types, which can be spatially patterned when incorporated into an adhesion and diffusion-enabled system.

Two distinct classes of prechondrogenic cell types in the embryonic limb bud

1983 ◽  
Vol 97 (1) ◽  
pp. 59-69 ◽  
Author(s):  
B.J. Swalla ◽  
E.M. Owens ◽  
T.F. Linsenmayer ◽  
M. Solursh
Keyword(s):  
Cell Types ◽  
Limb Bud ◽  
Embryonic Limb

scholarly journals Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration

Science ◽  
2018 ◽  
Vol 362 (6413) ◽  
pp. eaaq0681 ◽  
Author(s):  
Tobias Gerber ◽  
Prayag Murawala ◽  
Dunja Knapp ◽  
Wouter Masselink ◽  
Maritta Schuez ◽  
...  
Keyword(s):  
Single Cell ◽  
Messenger Rna ◽  
Single Cell Analysis ◽  
Limb Regeneration ◽  
Cell Types ◽  
Cellular Reprogramming ◽  
Limb Bud ◽  
Blastema Formation ◽  
Organ Regeneration ◽  
Embryonic Limb

Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of blastema formation had previously been hampered by the inability to identify and isolate blastema precursor cells in the adult tissue. We have used a combination of Cre-loxP reporter lineage tracking and single-cell messenger RNA sequencing (scRNA-seq) to molecularly track mature connective tissue (CT) cell heterogeneity and its transition to a limb blastema state. We have uncovered a multiphasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that recapitulates an embryonic limb bud–like phenotype including multipotency within the CT lineage. Together, our data illuminate molecular and cellular reprogramming during complex organ regeneration in a vertebrate.

Observations on the sorting-out of embryonic cells in monolayer culture

1975 ◽  
Vol 18 (3) ◽  
pp. 385-403
Author(s):  
M.S. Steinberg ◽  
D.R. Garrod
Keyword(s):  
Monolayer Culture ◽  
Cell Movement ◽  
Time Lapse ◽  
Cell Types ◽  
Liver Cells ◽  
Contact Inhibition ◽  
Limb Bud ◽  
Embryonic Cells ◽  
Embryo Cells ◽  
Embryonic Limb

Two problems are raised concerning the movement of cells during tissue-specific sorting-out of chick embryo cells in mixed aggregates. (i) A possible expectation from the hypothesis of ‘contact inhibition’ is that cells which are entirely surrounded by other cells in monolayer should be held stationary. Cells within solid aggregates, being totally surrounded by others, might also not be expected to move. How is it then that cell movement takes place within solid aggregates during sorting-out? (ii) Are the movements of cells within sorting aggregates ‘passive’, being driven by adhesive differentials or ‘active’, being merely guided by such differentials? In order to study these questions, sorting out experiments with chick embryonic limb bud mesenchyme and liver cells were carried out in monolayer culture, permitting direct observation of cell movements. Cell behavior was observed by time-lapse cinematography. Sorting-out of these cells in monolayer began before and continued after the cells had spread to confluency. During sorting, liver cells showed ruffing activity even when they appeared to be totally surrounded by other cells. Both cell types showed contact inhibition as judged by the criterion of monolayering, for they did not move over each other but remained attached to the substratum. Yet the cells in the confluent monolayer were not immobilized. Because of this, we suggest that the observed restraint against overlapping did not result from an inhibition of movement. Several considerations, detailed in the text, suggest that cell movement during sorting-out involve active locomotion. Previous work suggest that sorting-out configurations are determined by the relative intensities of intercellular adhesive strengths, the more cohesive of 2 cell populations tending to adopt the internal position. While limb bud cells form internal islands surrounded by liver cells in solid aggregates, the reverse was found to be the case in these monolayers. This suggests that, in the monolayer, limb bud cohesiveness is depressed relative to liver cell cohesiveness. This is consistent with the observation that the limb bud cells flattened themselves markedly against the substratum, significantly decreasing their area of mutual apposition.

Effects of EMP on Mouse Embryonic Limb Bud Cells

2006 ◽  
Author(s):  
Yongchun Zhou ◽  
Junye Liu ◽  
Guozhen Guo ◽  
Kangchu Li ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Limb Bud ◽  
Embryonic Limb

scholarly journals Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rongqun Guo ◽  
Mengdie Lü ◽  
Fujiao Cao ◽  
Guanghua Wu ◽  
Fengcai Gao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Cell ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Significant Difference ◽  
Cell Phenotypes ◽  
Acute Myeloid

Abstract Background Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components. Methods Using a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the immune cell phenotypes, function, and developmental trajectory of bone marrow (BM) samples from 16 AML patients and 4 healthy donors, but not AML blasts. Results We observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AML patients. We also identified several unique immune cell types including T helper cell 17 (TH17)-like intermediate population, cytotoxic CD4+ T subset, T cell: erythrocyte complexes, activated regulatory T cells (Treg), and CD8+ memory-like subset. Emerging AML cells remodels the BM immune microenvironment powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional immune effectors, expending immune-activated types, and promoting the formation of suppressive subsets. Conclusion Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.

scholarly journals The transcriptional tissue specificity of the human proα1(I) collagen gene is determined by a negative cis-regulatory element in the promoter

1992 ◽  
Vol 286 (1) ◽  
pp. 179-185 ◽  
Author(s):  
C P Simkevich ◽  
J P Thompson ◽  
H Poppleton ◽  
R Raghow
Keyword(s):  
Tissue Specificity ◽  
Regulatory Element ◽  
Mesenchymal Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Negative Influence ◽  
Collagen Gene ◽  
Specific Expression ◽  
Cis Acting ◽  
First Intron

The transcriptional activity of plasmid pCOL-KT, in which human pro alpha 1 (I) collagen gene upstream sequences up to -804 and most of the first intron (+474 to +1440) drive expression of the chloramphenicol acetyltransferase (CAT) gene [Thompson, Simkevich, Holness, Kang & Raghow (1991) J. Biol. Chem. 266, 2549-2556], was tested in a number of mesenchymal and non-mesenchymal cells. We observed that pCOL-KT was readily expressed in fibroblasts of human (IMR-90 and HFL-1), murine (NIH 3T3) and avian (SL-29) origin and in a human rhabdomyosarcoma cell line (A204), but failed to be expressed in human erythroleukaemia (K562) and rat pheochromocytoma (PC12) cells, indicating that the regulatory elements required for appropriate tissue-specific expression of the human pro alpha 1 (I) collagen gene were present in pCOL-KT. To delineate the nature of cis-acting sequences which determine the tissue specificity of pro alpha 1 (I) collagen gene expression, functional consequences of deletions in the promoter and first intron of pCOL-KT were tested in various cell types by transient expression assays. Cis elements in the promoter-proximal and intronic sequences displayed either a positive or a negative influence depending on the cell type. Thus deletion of fragments using EcoRV (nt -625 to -442 deleted), XbaI (-804 to -331) or SstII (+670 to +1440) resulted in 2-10-fold decreased expression in A204 and HFL-1 cells. The negative influences of deletions in the promoter-proximal sequences was apparently considerably relieved by deleting sequences in the first intron, and the constructs containing the EcoRV/SstII or XbaI/SstII double deletions were expressed to a much greater extent than either of the single deletion constructs. In contrast, the XbaI* deletion (nt -804 to -609), either alone or in combination with the intronic deletion, resulted in very high expression in all cells regardless of their collagen phenotype; the XbaI*/(-SstII) construct, which contained the intronic SstII fragment (+670 to +1440) in the reverse orientation, was not expressed in either mesenchymal or nonmesenchymal cells. Based on these results, we conclude that orientation-dependent interactions between negatively acting 5′-upstream sequences and the first intron determine the mesenchymal cell specificity of human pro alpha 1 (I) collagen gene transcription.

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

Combined developmental toxicity of bisphenol A and genistein in micromass cultures of rat embryonic limb bud and midbrain cells

2011 ◽  
Vol 25 (1) ◽  
pp. 153-159 ◽  
Author(s):  
Yang Xiao ◽  
Ran Liu ◽  
Lina Xing ◽  
Yajun Xu ◽  
Lanqin Shang ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Developmental Toxicity ◽  
Limb Bud ◽  
Embryonic Limb

scholarly journals Reaction-Diffusion Systems: Self-Balancing Diffusion and the Use of the Extent of Reaction as a Descriptor of Reaction Kinetics

2019 ◽  
Author(s):  
Miloslav Pekař
Keyword(s):  
Reaction Kinetics ◽  
Reaction Diffusion ◽  
Reaction Diffusion Systems ◽  
Diffusion Systems ◽  
And Diffusion ◽  
Reaction And Diffusion

Self-balancing diffusion is a concept which restricts the introduction of extents of reactions. This concept is analyzed in detail for mass- and molar-based balances of reaction-diffusion mixtures, in relation to non-self-balancing cases, and with respect to its practical consequences. A note on a recent generalization of the concept of reaction and diffusion extents is also included.<br>

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