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At least 91 records · Page 5Linked to original sources
PubMed2005

Prespore cell fate bias in G1 phase of the cell cycle in Dictyostelium discoideum.

By generating a population of Dictyostelium cells that are in the G1 phase of the cell cycle we have examined the influence of cell cycle status on cell fate specification, cell type proportioning and its regulation, and terminal differentiation. The lack of observable mitosis during the development of these cells and the quantification of their cellular DNA content suggests that they remain in G1 throughout development. Furthermore, chromosomal DNA synthesis was not detectable these cells, indicating that no synthesis phase had occurred, although substantial mitochondrial DNA synthesis did occur in prespore cells. The G1-phase cells underwent normal morphological development and sporulation but displayed an elevated prespore/prestalk ratio of 5.7 compared to the 3.0 (or 3:1) ratio normally observed in populations dominated by G2-phase cells. When migrating slugs produced by G1-phase cells were bisected, each half could reestablish the 5.7 (or 5.7:1) prespore/prestalk ratio. These results demonstrate that Dictyostelium cells can carry out the entire developmental cycle in the G1 phase of the cell cycle and that passage from G2 into G1 phase is not required for sporulation. Our results also suggest that the population asymmetry provided by the distribution of cells around the cell cycle at the time of starvation is not strictly required for cell type proportioning. Finally, when developed together with G2-phase cells, G1-phase cells preferentially become prespore cells and exclude G2-phase cells from the prespore-spore cell population, suggesting that G1-phase cells have an advantage over G2-phase cells in executing the spore cell differentiation pathway.

Animals↗
PubMed1995

Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate.

T cell-specific transcription factor (TCF-1) and lymphoid enhancer factor 1 (LEF-1) have been implicated exclusively in the regulation of T cell-specific genes. The only adult tissue other than thymus known to express these factors is spleen and lymph node, which contain low levels of LEF-1 and no TCF-1. We noticed that genes involved in hair-specific gene expression possess LEF-1/TCF-1 consensus motifs located in similar positions relative to their TATA box. We show that of the two factors only LEF-1 is expressed in hair follicles; it can be cloned in both splice forms from human skin keratinocytes and it can bind to these sites in the hair promoters. We show that LEF-1 mRNA is present in pluripotent ectoderm, and it is up-regulated in a highly restricted pattern just before the formation of underlying mesenchymal condensates and commitment of overlying ectodermal cells to invaginate and become hair follicles. New waves of ectodermal LEF-1 spots appear concomitant with new waves of follicle morphogenesis. To test whether LEF-1 patterning might be functionally important for hair patterning and morphogenesis, we used transgenic technology to alter the patterning and timing of LEF-1 over the surface ectoderm. Striking abnormalities arose in the positioning and orientation of hair follicles, leaving a marked disruption of this normally uniform patterning. This provides the first direct evidence that ectodermal cues are critical in establishing these developmental processes, which at later stages are known to be influenced by underlying mesenchyme. Remarkably, elevated LEF-1 in the lip furrow epithelium of developing transgenic animals triggered these cells to invaginate, sometimes leading to the inappropriate adoption of hair follicle and tooth cell fates. Collectively, our findings demonstrate that ectodermal expression of LEF-1 plays a central role in gene expression, pattern formation, and other developmental processes involving epithelial-mesenchymal associations.

Alternative Splicing↗
PubMed2004

Transient alteration of cell fate using a nuclear and cytoplasmic extract of an insulinoma cell line.

We report a transient modulation of cell fate in fibroblasts briefly exposed to an extract derived from the rat insulin-producing beta cell line, INS-1E. Primary fetal rat fibroblasts were reversibly permeabilized with Streptolysin O, incubated for 1h in a 15,000g INS-1E nuclear and cytoplasmic extract, resealed, and cultured. A first marker of change in cell fate was a reduction of cell and nuclear size within days of exposure to extract such that in some instances the fibroblasts resembled INS-1E cells. Second, two beta cell transcripts, Pdx-1 and insulin, were detected in the fibroblasts for up to 4 weeks. Third, (pro)insulin labeling was detected in 5-30% of the cells for a period of 8-14 days after incubation in extract. These phenotypes were absent from fibroblasts exposed to heat-treated INS-1E extracts, a human fibroblast cell line-derived extract or buffer. The results indicate that the extract of an insulinoma-derived cell line can promote at least a transient modification of cell fate towards a beta cell phenotype in non-beta cells. Because they are easily accessible, cell extracts may represent a practical source of material for investigating the mechanisms of alteration of a nuclear and cellular program.

Animals↗
PubMed2005

Contingent gene regulatory networks and B cell fate specification.

The B cell developmental pathway represents a leading system for the analysis of regulatory circuits that orchestrate cell fate specification and commitment. Considerable progress has been achieved within the past decade in the identification and genetic analysis of various regulatory components. These components include the transcription factors PU.1, Ikaros, Bcl11a, E2A, EBF, and Pax-5, as well as the cytokine receptors Flk2 and IL-7R. Experimental evidence of connectivity among the regulatory components is used to assemble sequentially acting and contingent gene regulatory networks. Transient signaling inputs, self-sustaining positive feedback loops, and cross-antagonism among alternate cell fate determinants are key features of the proposed networks that instruct the development of B lymphocyte precursors from hematopoietic stem cells.

Animals↗
PubMed2003

Myogenic cells fates are antagonized by Notch only in asymmetric lineages of the Drosophila heart, with or without cell division.

During the formation of the Drosophila heart, a combinatorial network that integrates signaling pathways and tissue-specific transcription factors specifies cardiac progenitors, which then undergo symmetric or asymmetric cell divisions to generate the final population of diversified cardiac cell types. Much has been learned concerning the combinatorial genetic network that initiates cardiogenesis, whereas little is known about how exactly these cardiac progenitors divide and generate the diverse population of cardiac cells. In this study, we examined the cell lineages and cell fate determination in the heart by using various cell cycle modifications. By arresting the cardiac progenitor cell divisions at different developing stages, we determined the exact cell lineages for most cardiac cell types. We found that once cardiac progenitors are specified, they can differentiate without further divisions. Interestingly, the progenitors of asymmetric cell lineages adopt a myocardial cell fate as opposed to a pericardial fate when they are unable to divide. These progenitors adopt a pericardial cell fate, however, when cell division is blocked in numb mutants or in embryos with constitutive Notch activity. These results suggest that a numb/Notch-dependent cell fate decision can take place even in undivided progenitors of asymmetric cell divisions. By contrast, in symmetric lineages, which give rise to a single type of myocardial-only or pericardial-only progeny, repression or constitutive activation of the Notch pathway has no apparent effect on progenitor or progeny fate. Thus, inhibition of Notch activity is crucial for specifying a myogenic cell fate only in asymmetric lineages. In addition, we provide evidence that whether or not Suppressor-of-Hairless can become a transcriptional activator is the key switch for the Numb/Notch activity in determining a myocardial versus pericardial cell fate.

Animals↗
PubMed1999

Comparison of ES cell fate in sandwiched aggregates and co-cultured aggregates during blastocyst formation by monitored GFP expression.

Markers and the means to detect them are required to monitor the fate of living cells. However, few suitable markers for living cells were known until a green fluorescent protein (GFP) was discovered. We have established mouse embryonic stem (ES) cell lines that express mutant GFP under the chicken beta-actin (CAG) promoter. Using these cell lines, we were able to follow the migration of ES cells during blastocyst formation both in sandwiching and coculture methods, even if only a single ES cell was used. Furthermore, the contribution of ES cells to the inner cell mass (ICM) was easily estimated at the blastocyst stage. We compared sandwiching with coculture aggregation relative to the contribution of the ES cell in the ICM, and the results indicated that there was no difference in the ratios of chimeric embryos having ICM contributed from cultured ES cells. Furthermore, an aggregated single ES cell was able to contribute three or four cells to the ICM at the blastocyst stage. Thus we conclude that one, instead of two, embryos is enough to make aggregation with ES cells, and a single ES cell attached to an embryo is enough to produce germline chimeras. Moreover, we could clearly observe single cell fate during blastocyst formation. This suggests that our established cell line can be used for monitoring single cell fate in vivo. In addition, we have shown that up to five doses of 30 sec of UV irradiation using GFP filters have no effect on the embryonic development.

Animals↗
PubMed2001

Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division.

Cell-fate diversity is generated in part by the unequal segregation of cell-fate determinants during asymmetric cell divisions. In the Drosophila pupa, the pI sense organ precursor cell is polarized along the anterior-posterior axis of the fly and divides asymmetrically to generate a posterior pIIa cell and an anterior pIIb cell. The anterior pIIb cell specifically inherits the determinant Numb and the adaptor protein Partner of Numb (Pon). By labelling both the Pon crescent and the microtubules in living pupae, we show that determinants localize at the anterior cortex before mitotic-spindle formation, and that the spindle forms with random orientation and rotates to line up with the Pon crescent. By imaging living frizzled (fz) mutant pupae we show that Fz regulates the orientation of the polarity axis of pI, the initiation of spindle rotation and the unequal partitioning of determinants. We conclude that Fz participates in establishing the polarity of pI.

Animals↗
PubMed1997

Drosophila mitotic domain boundaries as cell fate boundaries.

Fate determination in Drosophila embryos is evidenced by the appearance of mitotic domains. To identify fate or fates of cells, individual cells in mitotic domains 2, 8, and 15 were marked and monitored through development. Comparison of the different fates indicated that domain boundaries are cell fate boundaries. Cells were marked by expression of GAL4-dependent transgenes after photoactivation of a caged GAL4VP16 analog that had its DNA binding activity inhibited with a photolabile blocking reagent. Caged GAL4VP16 was also used to induce gene expression in Xenopus embryos. Thus, photoactivated gene expression is a versatile tool for spatiotemporal control of gene expression.

Animals↗
PubMed1999

Regulative development in a nematode embryo: a hierarchy of cell fate transformations.

Cell specification during embryogenesis of the model system Caenorhabditis elegans involves a combination of inductive and autonomous mechanisms. We have begun to study the development of other nematodes to investigate how well cell-specification mechanisms are preserved among closely related species. Here we report that the embryo of the soil nematode Acrobeloides nanus expresses a so far undescribed regulative potential. When, for instance, the first somatic founder cell AB is eliminated it is replaced by its posterior neighbor EMS, which in turn is replaced by the C cell. This allows-different from C. elegans-the development of partial embryos up to hatching and sometimes to fertile adults. Thus, early somatic blastomeres in A. nanus are multipotent, each being capable of giving rise to more than one somatic founder cell. Lost germ-line cells, however, are not replaced. A model is presented, according to which in A. nanus cellular identities are assigned by specific reciprocal inhibitory cell-cell interactions absent in C. elegans. Differences and similarities in cell specification between the two species are discussed and related to different developmental strategies.

Animals↗
PubMed2006

Cellular conference call: external feedback affects cell-fate decisions.

Cells often need to respond to multiple opposing signals simultaneously. In this issue of Cell, it is shown that challenging cells with multiple extracellular signals induces an external feedback that involves the release of and response to additional secreted factors with antagonistic functions. These results suggest that an individual cell's decision to die or survive is not wholly independent but depends, at least in part, on feedback from its neighbors.

Animals↗
PubMed1999

Filopodia: fickle fingers of cell fate?

Epithelial cells often produce extensions, known variously as filopodia, cell feet or cytonemes, which can extend across many cell diameters to directly contact non-adjacent cells. Do they function in morphogenesis, cell-cell signaling or both?.

Animals↗
PubMed2004

Stem cell leukemia protein directs hematopoietic stem cell fate.

Stem cell leukemia (SCL) protein has been shown to be an essential transcription factor during hematopoietic development in the embryo. In adult hematopoiesis, however, the role for SCL has remained largely unknown, whereas it is expressed in bone marrow hematopoietic stem cells (HSCs). In this study, we performed HSC transplantation and an in vitro HSC differentiation assay using retrovirally transduced HSCs with wild-type (WT) and dominant-negative (DN) SCL. The transplantation experiments showed that SCL does not affect the long-term repopulating capacity of HSCs but that WT SCL and DN SCL increase the short-term contribution of the transduced HSCs in myeloid and lymphoid lineages, respectively. An in vitro single-cell assay using a fetal thymus organ culture system further demonstrated that WT SCL facilitates HSCs to differentiate into the myeloid lineage but that DN SCL facilitates HSCs to differentiate into the lymphoid lineage. We conclude that the up-regulation or down-regulation of SCL directs HSCs toward myeloid or lymphoid lineage, respectively, although SCL does not affect their long-term repopulating capacity.

Animals↗
PubMed2003

Engineered zinc finger proteins for controlling stem cell fate.

Stem cells are functionally defined as progenitor cells that can self-renew and differentiate. Critical transitions in these cells are controlled via signaling pathways and subsequent transcriptional regulation. Technologies capable of modulating the levels of gene expression, especially those of transcription factors, represent powerful tools for research and could potentially be used in therapeutic applications. In this study, we evaluated the ability of synthetic zinc finger protein transcription factors (ZFP-TFs) to cause the differentiation of embryonic stem (ES) cells. We constructed ZFP-TFs that target the mouse Oct-4 gene (which is a major regulator of ES cell pluripotency and self-renewal). These designed transcription factors were able to regulate the transcription of Oct-4, affecting the expression of downstream genes and thus regulating ES cell differentiation.

Animals↗
PubMed1998

The Arabidopsis thaliana gametophytic mutation gemini pollen1 disrupts microspore polarity, division asymmetry and pollen cell fate.

Pollen development and male gametogenesis are critically dependent upon cell polarization leading to a highly asymmetric cell division termed pollen mitosis I. A mutational approach was adopted in Arabidopsis thaliana to identify genes involved these processes. Four independent gemini pollen mutants were isolated which produce divided or twin-celled pollen. The gemini pollen1 mutant was characterized in detail and shown to act gametophytically resulting in reduced transmission through both sexes. gemini pollen1 showed an incompletely penetrant phenotype resulting in equal, unequal and partial divisions at pollen mitosis I. The division planes in gemini pollen1 were shown to be aligned with the polar axis (as in wild type) and evidence was obtained for incomplete nuclear migration, which could account for altered division symmetry. gemini pollen1 also showed division phenotypes consistent with spatial uncoupling of karyokinesis and cytokinesis suggesting that GEMINI POLLEN1 may be required for the localization of phragmoplast activity. Cell fate studies showed that in both equal and unequal divisions a vegetative cell marker gene was activated in both daughter cells. Daughter cells with a range of intermediate or hybrid vegetative/generative cell fates suggests that cell fate is quantitatively related to cell size. The potential mode of action of GEMINI POLLEN1 and its effects on cell fate are discussed in relation to proposed models of microspore polarity and cell fate determination.

Arabidopsis↗
PubMed1995

Regionalisation of cell fate and morphogenetic movement of the mesoderm during mouse gastrulation.

The developmental fate of cells in the epiblast of early-primitive-streak-stage mouse embryos was assessed by studying the pattern of tissue colonisation displayed by lac Z-expressing cells grafted orthotopically to nontransgenic embryos. Results of these fate-mapping experiments revealed that the lateral and posterior epiblast contain cells that will give rise predominantly to mesodermal derivatives. The various mesodermal populations are distributed in overlapping domains in the lateral and posterior epiblast, with the embryonic mesoderm such as heart, lateral, and paraxial mesoderm occupying a more distal position than the extraembryonic mesoderm. Heterotopic grafting of presumptive mesodermal cells results in the grafted cells adopting the fate appropriate to the new site, reflecting a plasticity of cell fate determination before ingression. The first wave of epiblast cells that ingress through the primitive streak are those giving rise to extraembryonic mesoderm. Cells that will form the mesoderm of the yolk sac and the amnion make up a major part of the mesodermal layer of the midprimitive-streak-stage embryo. Cells that are destined for embryonic mesoderm are still found within the epiblast, but some have been recruited to the distal portion of the mesoderm. By the late-primitive-streak-stage, the mesodermal layer contains only the precursors of embryonic mesoderm. This suggests that there has been a progressive displacement of the midstreak mesoderm to extraembryonic sites, which is reminiscent of that occurring in the overlying endodermal tissue. The regionalisation of cell fate in the late-primitive-streak mesoderm bears the same spatial relationship as their ancestors in the epiblast prior to cell ingression. This implies that both the position of the cells in the proximal-distal axis and their proximity to the primitive streak are major determinants for the patterning of the embryonic mesoderm.

Animals↗
PubMed1995

Lateral specification of cell fate during vertebrate development.

Cells within equivalence groups interact via lateral specification to determine cell fates during development in Caenorhabditis elegans and other invertebrates. Populations of cells within the developing zebrafish have features similar to those of invertebrate equivalence groups. In a simple example, two identified zebrafish motoneurons behave as an equivalence pair in which one cell adopts a primary fate and interactions between the cells assign the other cell to a secondary fate. A more complicated situation exists for two initially equivalent populations of zebrafish neural crest cells. We consider whether mechanisms similar to those involved in fate specification within invertebrate equivalence groups also function furing fate specification in vertebrates.

Animals↗
PubMed2004

Signal processing underlying extrinsic control of stem cell fate.

PURPOSE OF REVIEW: Strategies to manipulate stem cells for therapeutic applications are limited by our inability to control or predict stem cell fate decisions in response to exogenous stimuli. This review focuses on the mechanisms by which exogenous stimuli influence cell fate. RECENT FINDINGS: Limitations in our ability to control cell fate arises from our primarily qualitative understanding of stem cell regulation, which proposes straightforward cue-fate relationships that appear to be the exception rather than the rule. Alternatively, consideration of the underlying quantitative, temporal, and spatial mechanisms governing extrinsic regulation of stem cell fate may enable novel approaches to control stem cell output predictively. SUMMARY: The authors review advances in the understanding of these underlying mechanisms, and discuss experimental and analytic tools necessary to investigate and use these mechanisms to control stem cell fate.

Animals↗
PubMed2002

Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells.

RBP-J is a key mediator of Notch signaling that regulates cell fate determination in various lineages. To investigate the function of Notch-RBP-J in mature B cell differentiation, we generated mice that selectively lacked B cell RBP-J expression using conditional mutagenesis. Absence of RBP-J led to the loss of marginal zone B (MZB) cells with a concomitant increase in follicular B cells; in contrast, B1 cells in the peritoneal cavity were unaffected. Lack of RBP-J caused no defects in B cells maintenance, survival, plasma cell differentiation or activation. It is therefore likely that Notch-RBP-J signaling regulates the lineage commitment of mature B cells into follicular versus MZB cells. In addition, in mice with RBP-J-deficient B cells, had no obvious changes in immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken gammaglobulin. In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria.

Animals↗