Early determination in the C. elegans embryo: a gene, cib-1, required to specify a set of stem-cell-like blastomeres

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 107-119 ◽  
Author(s):  
R. Schnabel ◽  
H. Schnabel
Keyword(s):  
Cell Cycle ◽  
Decision Making ◽  
Stem Cell ◽  
Early Embryo ◽  
Cell Cycles ◽  
C Elegans ◽  
Lethal Mutations ◽  
A Cell ◽  
Early Decision ◽  
P Cells

The early somatic blastomeres founding the tissues in the C. elegans embryo are derived in a stem-cell-like lineage from the P cells. We have isolated maternal effect lethal mutations defining the gene cib-1 in which the P cells, P1-P3, skip a cell cycle and acquire the fates of only their somatic daughters. Therefore, the cib-1 gene is required for the specification of the stem-cell-like fate of these cells. The analysis of the development of these mutants suggests that the clock controlling the cell cycles in the early embryo is directly coupled to the fate of a cell and that there must be another developmental clock that activates the determinative inventory for the early decision-making.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

Abstract An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

scholarly journals A molecular marker for centriole maturation in the mammalian cell cycle.

1995 ◽  
Vol 130 (4) ◽  
pp. 919-927 ◽  
Author(s):  
B M Lange ◽  
K Gull
Keyword(s):  
Cell Cycle ◽  
Molecular Marker ◽  
Specific Cell ◽  
Cell Cycles ◽  
Functional Maturation ◽  
Ability To Act ◽  
Molecular Events ◽  
Mammalian Cell Cycle ◽  
A Cell ◽  
First Time

The centriole pair in animals shows duplication and structural maturation at specific cell cycle points. In G1, a cell has two centrioles. One of the centrioles is mature and was generated at least two cell cycles ago. The other centriole was produced in the previous cell cycle and is immature. Both centrioles then nucleate one procentriole each which subsequently elongate to full-length centrioles, usually in S or G2 phase. However, the point in the cell cycle at which maturation of the immature centriole occurs is open to question. Furthermore, the molecular events underlying this process are entirely unknown. Here, using monoclonal and polyclonal antibody approaches, we describe for the first time a molecular marker which localizes exclusively to one centriole of the centriolar pair and provides biochemical evidence that the two centrioles are different. Moreover, this 96-kD protein, which we name Cenexin (derived from the Latin, senex for "old man," and Cenexin for centriole) defines very precisely the mature centriole of a pair and is acquired by the immature centriole at the G2/M transition in prophase. Thus the acquisition of Cenexin marks the functional maturation of the centriole and may indicate a change in centriolar potential such as its ability to act as a basal body for axoneme development or as a congregating site for microtubule-organizing material.

scholarly journals The evaluation of proliferation ability of cardiomyocytes in heart failure

2021 ◽  
Vol 271 ◽  
pp. 03064
Author(s):  
Mengzi Gao
Keyword(s):  
Heart Failure ◽  
Cell Cycle ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Rna Seq ◽  
Cell Cycles ◽  
A Cell ◽  
Proliferation Ability ◽  
Heat Failure

The proliferation ability of cardiomyocytes is always under a controversial situation, especially under some stress condition such as heart failure disease and external damages. Heat failure (HF) is a complex clinical syndrome that results from left ventricular myocardial dysfunction and contributes to dyspnea, fatigue and fluid retention. The proliferation ability is related to the cell cycles and lot of cell-cycle related genes are involved in the evaluation of proliferation ability of cardiomyocytes. RNA-seq is a quite common technique in evaluate the transcription expression pattern of genes in many studies. Here in our article we analyzed the existing RNA-seq dataset to evaluate the mRNA expression level of several genes which can be indicators of the activity of cell cycles. We found that the cyclin D2 which is a cell cycle activator is upregulated in dilated cardiomyopathy (DCM) disease, indicating that the proliferation ability may be higher in DCM heart. The results throw light on the proliferation research of adult cardiomyocytes.

scholarly journals Impact of Global Transcriptional Silencing on Cell Cycle Regulation and Chromosome Segregation in Early Mammalian Embryos

2021 ◽  
Vol 22 (16) ◽  
pp. 9073
Author(s):  
Martin Anger ◽  
Lenka Radonova ◽  
Adela Horakova ◽  
Diana Sekach ◽  
Marketa Charousova
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Significant Proportion ◽  
Transcriptional Silencing ◽  
Early Embryo ◽  
Global Changes ◽  
Embryonic Genome ◽  
Mammalian Embryos ◽  
A Cell ◽  
And Behavior

The onset of an early development is, in mammals, characterized by profound changes of multiple aspects of cellular morphology and behavior. These are including, but not limited to, fertilization and the merging of parental genomes with a subsequent transition from the meiotic into the mitotic cycle, followed by global changes of chromatin epigenetic modifications, a gradual decrease in cell size and the initiation of gene expression from the newly formed embryonic genome. Some of these important, and sometimes also dramatic, changes are executed within the period during which the gene transcription is globally silenced or not progressed, and the regulation of most cellular activities, including those mentioned above, relies on controlled translation. It is known that the blastomeres within an early embryo are prone to chromosome segregation errors, which might, when affecting a significant proportion of a cell within the embryo, compromise its further development. In this review, we discuss how the absence of transcription affects the transition from the oocyte to the embryo and what impact global transcriptional silencing might have on the basic cell cycle and chromosome segregation controlling mechanisms.

scholarly journals Modeling the C. elegans Germline Stem Cell Genetic Network using Automated Reasoning

2021 ◽  
Author(s):  
Ani Amar ◽  
E. Jane Albert Hubbard ◽  
Hillel Kugler
Keyword(s):  
Decision Making ◽  
Stem Cell ◽  
Germ Line ◽  
Genetic Network ◽  
Genetic Networks ◽  
Genetic Interactions ◽  
Formal Reasoning ◽  
Regulatory Interactions ◽  
C Elegans ◽  
Cellular Decision Making

Computational methods and tools are a powerful complementary approach to experimental work for studying regulatory interactions in living cells and systems. We demonstrate the use of formal reasoning methods as applied to the Caenorhabditis elegans germ line, which is an accessible model system for stem cell research. The dynamics of the underlying genetic networks and their potential regulatory interactions are key for understanding mechanisms that control cellular decision making between stem cells and differentiation.We model the 'stem cell fate' versus entry into the 'meiotic development' pathway decision circuit in the young adult germ line based on an extensive study of published experimental data and known/hypothesized genetic interactions. We apply a formal reasoning framework to derive predictive networks for control of differentiation. Using this approach we simultaneously specify many possible scenarios and experiments together with potential genetic interactions, and synthesize genetic networks consistent with all encoded experimental observations. In silico analysis of knock-down and overexpression experiments within our model recapitulate published phenotypes of mutant animals and can be applied to make predictions on cellular decision-making. This work lays a foundation for developing realistic whole tissue models of the C. elegans germ line where each cell in the model will execute a synthesized genetic network.

scholarly journals Cyclin Cln3p Links G1 Progression to Hyphal and Pseudohyphal Development in Candida albicans

2005 ◽  
Vol 4 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Catherine Bachewich ◽  
Malcolm Whiteway
Keyword(s):  
Cell Cycle ◽  
Candida Albicans ◽  
Critical Role ◽  
Growth Conditions ◽  
Yeast Cells ◽  
Independent Manner ◽  
Cell Cycles ◽  
Environmental Controls ◽  
A Cell ◽  
Synthetically Lethal

ABSTRACT G1 cyclins coordinate environmental conditions with growth and differentiation in many organisms. In the pathogen Candida albicans, differentiation of hyphae is induced by environmental cues but in a cell cycle-independent manner. Intriguingly, repressing the G1 cyclin Cln3p under yeast growth conditions caused yeast cells to arrest in G1, increase in size, and then develop into hyphae and pseudohyphae, which subsequently resumed the cell cycle. Differentiation was dependent on Efg1p, Cph1p, and Ras1p, but absence of Ras1p was also synthetically lethal with repression of CLN3. In contrast, repressing CLN3 in environment-induced hyphae did not inhibit growth or the cell cycle, suggesting that yeast and hyphal cell cycles may be regulated differently. Therefore, absence of a G1 cyclin can activate developmental pathways in C. albicans and uncouple differentiation from the normal environmental controls. The data suggest that the G1 phase of the cell cycle may therefore play a critical role in regulating hyphal and pseudohyphal development in C. albicans.

scholarly journals CONDITIONAL MUTANTS IN CHLAMYDOMONAS REINHARDTII BLOCKED IN THE VEGETATIVE CELL CYCLE

1973 ◽  
Vol 57 (3) ◽  
pp. 760-772 ◽  
Author(s):  
Stephen H. Howell ◽  
Jay A. Naliboff
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chlamydomonas Reinhardtii ◽  
Simple Technique ◽  
Restrictive Temperature ◽  
Permissive Temperature ◽  
General Applicability ◽  
Cell Cycles ◽  
Point Analysis ◽  
A Cell

Conditional "cycle-blocked" (cb) mutants of Chlamydomonas reinhardtii have been detected and isolated. These mutants exhibit normal vegetative growth at permissive temperature but are unable to complete a cell cycle (or a specified number of cell cycles) at restrictive temperature. A simple technique has been devised to determine the cell cycle stage in each mutant when the defective gene product, which ultimately affects cell division, completes its function. This stage is called the "block point", and is determined by scoring the residual cell division in an exponentially growing population after shift to temperature restrictive conditions. In the cb mutants isolated so far, block points representing many stages throughout the cell cycle have been found. Two categories of cb mutants are described here: one set which prevents the subsequent cell division when the cell encounters the block point after a shift to restrictive temperature, and another set which permits an additional round of cell division after the block point is encountered. The general applicability of block point analysis to other cell systems is presented.

Characterization of the unusually rapid cell cycles during rat gastrulation

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 873-883 ◽  
Author(s):  
A. Mac Auley ◽  
Z. Werb ◽  
P.E. Mirkes
Keyword(s):  
Cell Cycle ◽  
Cycle Time ◽  
Mammalian Cells ◽  
Primitive Streak ◽  
Cycle Duration ◽  
Embryonic Cells ◽  
Cell Cycle Time ◽  
Cell Cycles ◽  
A Cell ◽  
Cycle Regulation

The onset of gastrulation in rodents is associated with the start of differentiation within the embryo proper and a dramatic increase in the rate of growth and proliferation. We have determined the duration of the cell cycle for mesodermal and ectodermal cells of rat embryos during gastrulation (days 8.5 to 9.5 of gestation) using a stathmokinetic analysis. These embryonic cells are the most rapidly dividing mammalian cells yet described. Most cells of the ectoderm and mesoderm had a cell cycle time of 7 to 7.5 hours, but the cells of the primitive streak divided every 3 to 3.5 hours. Total cell cycle time was reduced by shortening S and G2, as well as G1, in contrast to cells later in development, when cell cycle duration is modulated largely by varying the length of G1. In the ectoderm and mesoderm, G1 was 1.5 to 2 hours, S was 3.5 to 4 hours, and G2 was 30 to 40 minutes. G1, S and G2 were shortened even further in the cells of the primitive streak: G1 was less than 30 minutes, S was 2 to 2.75 hours, and G2 was less than 20 minutes. Thus, progress of cells through all phases of the cell cycle is extensively modified during rodent embryogenesis. Specifically, the increased growth rate during gastrulation is associated with radical changes in cell cycle structure and duration. Further, the commitment of cells to become mesoderm and endoderm by entering the primitive streak is associated with expression of a very short cell cycle during transit of the primitive streak, such that developmental decisions determining germ layer fate are reflected in differences in cell cycle regulation.

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