Live-imaging of single stem cells within their niche reveals that a U3snoRNP component segregates asymmetrically and is required for self-renewal in Drosophila

Fichelson, Pierre; Moch, Clara; Ivanovitch, Kenzo; Martin, Charlotte; Sidor, Clara; Lepesant, Jean‐Antoine; Bellaı̈che, Yohanns; Huynh, Jean‐René

doi:10.1038/ncb1874

Cited by 78 publications

(79 citation statements)

References 51 publications

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“…Migration and hybridization were performed as previously described. 63 The probes used in this study were Its1-1a (5ʹ-ACGCCGCCGCTCCTCCACAGTCTCCCGTT-3ʹ) and Its2-2 (5ʹ-ACTGGTGAGG CAGCGGTCCGGGAGGCGCCGACG-3ʹ).…”

Section: Discussionmentioning

confidence: 99%

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

et al. 2015

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International audienceRibosome biogenesis is an essential cellular process. Its impairment is associated with developmental defects and increased risk of cancer. The in vivo cellular responses to defective ribosome biogenesis and the underlying molecular mechanisms are still incompletely understood. In particular, the consequences of impaired ribosome biogenesis within the intestinal epithelium in mammals have not been investigated so far. Here we adopted a genetic approach to investigate the role of Notchless (NLE), an essential actor of ribosome biogenesis, in the adult mouse intestinal lineage. Nle deficiency led to defects in the synthesis of large ribosomal subunit in crypts cells and resulted in the rapid elimination of intestinal stem cells and progenitors through distinct types of cellular responses, including apoptosis, cell cycle arrest and biased differentiation toward the goblet cell lineage. Similar observations were made using the rRNA transcription inhibitor CX-5461 on intestinal organoids culture. Importantly, we found that p53 activation was responsible for most of the cellular responses observed, including differentiation toward the goblet cell lineage. Moreover, we identify the goblet cell-specific marker Muc2 as a direct transcriptional target of p53. Nle-deficient ISCs and progenitors disappearance persisted in the absence of p53, underlying the existence of p53-independent cellular responses following defective ribosome biogenesis. Our data indicate that NLE is a crucial factor for intestinal homeostasis and provide new insights into how perturbations of ribosome biogenesis impact on cell fate decisions within the intestinal epithelium

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Section: Discussionmentioning

confidence: 99%

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

et al. 2015

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“…A molecular mechanism driving asymmetric chromosomal segregation has not yet been elucidated in any cell type or organism. Several hypotheses have been generated, including the recognition of DNA methylation sites, chromatin patterns, histones, ribosomal synthesis, and microtubule/ centrosomal assemblies (4,40). The next challenge is to determine how dysregulation of these putative mechanisms may participate in template DNA recognition, as well as self-renewal, in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Microenvironmental modulation of asymmetric cell division in human lung cancer cells

Pine

Ryan²,

Varticovski³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

128

148

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Normal tissue homeostasis is maintained through asymmetric cell divisions that produce daughter cells with differing self-renewal and differentiation potentials. Certain tumor cell subfractions can self-renew and repopulate the heterogeneous tumor bulk, suggestive of asymmetric cell division, but an equally plausible explanation is that daughter cells of a symmetric division subsequently adopt differing cell fates. Cosegregation of template DNA during mitosis is one mechanism by which cellular components are segregated asymmetrically during cell division in fibroblast, muscle, mammary, intestinal, and neural cells. Asymmetric cell division of template DNA in tumor cells has remained elusive, however. Through pulsechase experiments with halogenated thymidine analogs, we determined that a small population of cells within human lung cancer cell lines and primary tumor cell cultures asymmetrically divided their template DNA, which could be visualized in single cells and in real time. Template DNA cosegregation was enhanced by cell-cell contact. Its frequency was density-dependent and modulated by environmental changes, including serum deprivation and hypoxia. In addition, we found that isolated CD133+ lung cancer cells were capable of tumor cell repopulation. Strikingly, during cell division, CD133 cosegregated with the template DNA, whereas the differentiation markers prosurfactant protein-C and pan-cytokeratins were passed to the opposing daughter cell, demonstrating that segregation of template DNA correlates with lung cancer cell fate. Our results demonstrate that human lung tumor cell fate decisions may be regulated during the cell division process. The characterization and modulation of asymmetric cell division in lung cancer can provide insight into tumor initiation, growth, and maintenance.cancer stem cell | CD133 | immortal DNA | template DNA

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“…While some of the reported deficiency alleles created by this method have later been shown to not actually create a deficiency, at least two lines of evidence support Df7142 as an actual deficiency allele (Cook 2012). First, it has previously been tested in a complementation assay with an allele of wcd, a gene expected to be deleted in Df7142, and failed to complement this mutation (Fichelson et al, 2009). Secondly, the abundance of Sema-2b RNA in embryos of a Df7142/CyO line was tested by qRT-PCR and found to be significantly less than that of wildtype embryos (P < 0.05).…”

Section: Loss-of-function Alleles Of Sema-2b Cause Specific Motoneuromentioning

confidence: 99%

Drosophila semaphorin2b is required for the axon guidance of a subset of embryonic neurons

Emerson

Long

Vactor

2013

Developmental Dynamics

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Background: The process of axon guidance is important in establishing functional neural circuits. The differential expression of cell-autonomous axon guidance factors is crucial for allowing axons of different neurons to take unique trajectories in response to spatially and temporally restricted cell non-autonomous axon guidance factors. A key motivation in the field is to provide adequate explanations for axon behavior with respect to the differential expression of these factors. Results: We report the characterization of a predicted secreted semaphorin family member, semaphorin2b (Sema-2b) in Drosophila embryonic axon guidance. Misexpression of Sema-2b in neurons causes highly penetrant axon guidance phenotypes in specific longitudinal and motoneuron pathways; however, expression of Sema-2b in muscles traversed by these motoneurons has no effect on axon guidance. In Sema-2b loss-of-function embryos, specific motoneuron and interneuron axon pathways display guidance defects. Specific visualization of the neurons that normally express Sema-2b reveals that this neuronal cohort is strongly affected by Sema-2b loss-offunction alleles. Conclusions: While secreted semaphorins have been implicated as cell non-autonomous chemorepellants in a variety of contexts, here we report previously undescribed Sema-2b loss-of-function and misexpression phenotypes that are consistent with a cell-autonomous role for Sema-2b. Developmental Dynamics 242:861-873, 2013. V C 2013 Wiley Periodicals, Inc.Key words: Drosophila; axon guidance; semaphorin Key Findings:Misexpression of the secreted semaphorin Sema-2b in neurons results in specific axon guidance phenotypes. Both Sema-2b loss-of-function and misexpression phenotypes are congruent with a cell-autonomous role for Sema-2b. Novel axon guidance phenotypes caused by Sema-2b loss-of-function mutations are characterized.

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Live-imaging of single stem cells within their niche reveals that a U3snoRNP component segregates asymmetrically and is required for self-renewal in Drosophila

Cited by 78 publications

References 51 publications

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells

Microenvironmental modulation of asymmetric cell division in human lung cancer cells

Drosophila semaphorin2b is required for the axon guidance of a subset of embryonic neurons

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