Neuroblasts: a model for the asymmetric division of stem cells

Lin, Haifan; Schagat, Trista

doi:10.1016/s0168-9525(96)10050-0

Cited by 83 publications

(43 citation statements)

References 42 publications

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“…The growth characteristics of the SP subpopulation also were consistent with the predicted behavior of primitive precursor cells, including a high proliferative rate and self-renewal capacity (13,14). Hoechst low SP and Hoechst high non-SP cells (SK-N-SH, IMR-32, and JF lines) were separated by flow cytometry, and equal numbers of cells from both subpopulations were cultured in vitro.…”

Section: Resultssupporting

confidence: 64%

A distinct “side population” of cells with high drug efflux capacity in human tumor cells

Hirschmann-Jax

Foster

Wulf

et al. 2004

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

1,166

1,030

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A subset of stem cells, termed the ''side population'' (SP), has been identified in several tissues in mammalian species. These cells maintain a high efflux capability for antimitotic drugs. We have investigated whether functionally equivalent stem cells also may be detected in human cancers. We initially examined primary tumor cells from 23 patients with neuroblastoma and cell lines derived from a range of other tumors. A distinct SP was found in neuroblastoma cells from 15 of 23 patients (65%). The SP was capable of sustained expansion ex vivo and showed evidence for asymmetric division, generating both SP and non-SP progeny. These cells also expressed high levels of ABCG2 and ABCA3 transporter genes and had a greater capacity to expel cytotoxic drugs, such as mitoxantrone, resulting in better survival. A SP also was detected in breast cancer, lung cancer, and glioblastoma cell lines, suggesting that this phenotype defines a class of cancer stem cells with inherently high resistance to chemotherapeutic agents that should be targeted during the treatment of malignant disease.

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Section: Resultssupporting

confidence: 64%

A distinct “side population” of cells with high drug efflux capacity in human tumor cells

Hirschmann-Jax

Foster

Wulf

et al. 2004

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

1,166

1,030

View full text Add to dashboard Cite

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“…The ability of stem cells to self-renew and to produce a large number of differentiated progeny is critical for the development and maintenance of a wide variety of tissues in organisms ranging from insects to mammals (for review, see Lin 1997;Lin and Schagat 1997;Morrison et al 1997;Potten 1997). This self-renewing ability is controlled both by extrinsic signaling and by cell-autonomous mechanisms (for review, see Lin and Schagat 1997;Morrison et al 1997).…”

mentioning

confidence: 99%

“…This self-renewing ability is controlled both by extrinsic signaling and by cell-autonomous mechanisms (for review, see Lin and Schagat 1997;Morrison et al 1997). Cell-autonomous mechanisms have been elucidated in a few stem cell models such as neuroblasts and germ-line stem cells (GSC) in Drosophila (Deng and Lin 1997;Lin and Schagat 1997), whereas the role of extrinsic signaling in controlling stem cell division has been implicated in several systems (Morrison et al 1997). For example, the proliferation and differentiation of mammalian stem cells in the hematopoietic, epidermal, and nervous systems depend on extrinsic signals that act on specific receptors on the stem cell surface (Morrison et al 1997).…”

mentioning

confidence: 99%

A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal

Cox¹,

Chao²,

Baker³

et al. 1998

Genes Dev.

Self Cite

901

819

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Germ-line stem cells (GSCs) serve as the source for gametogenesis in diverse organisms. We cloned and characterized the Drosophila piwi gene and showed that it is required for the asymmetric division of GSCs to produce and maintain a daughter GSC but is not essential for the further differentiation of the committed daughter cell. Genetic mosaic and RNA in situ analyses suggest that piwi expression in adjacent somatic cells regulates GSC division. piwi encodes a highly basic novel protein, well conserved during evolution. We isolated piwi homologs in Caenorhabditis elegans and humans and also identified Arabidopsis piwi-like genes known to be required for meristem cell maintenance. Decreasing C. elegans piwi expression reduces the proliferation of GSC-equivalent cells. Thus, piwi represents a novel class of genes required for GSC division in diverse organisms.

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“…Shortly after their arrival, most NBs initiate a series of 5-10 asymmetric divisions, producing a progenitor cell with each eventthe ganglion mother cell (GMC). GMC divisions yield either neurons or glia (for reviews, see Campos-Ortega 1993;Goodman and Doe 1993;Lin and Schagat 1997).…”

mentioning

confidence: 99%

Regulation of POU genes by castor andhunchback establishes layered compartments in theDrosophila CNS

Kambadur¹,

Koizumi²,

Stivers³

et al. 1998

Genes Dev.

262

242

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POU transcription factors participate in cell-identity decisions during nervous system development, yet little is known about the regulatory networks controlling their expression. We report all known Drosophila POU genes require castor (cas) for correct CNS expression. drifter and I-POU depend on cas for full expression, whereas pdm-1 and pdm-2 are negatively regulated. cas encodes a zinc finger protein that shares DNA-binding specificity with another pdm repressor: the gap segmentation gene regulator Hunchback (Hb). Our studies reveal that the embryonic CNS contains sequentially generated neuroblast sublineages that can be distinguished by their expression of either Hb, Pdm-1, or Cas. Hb and Cas may directly silence pdm expression in early and late developing sublineages, given that pdm-1 cis-regulatory DNA contains у32 Hb/Cas-binding sites and its enhancer(s) are ectopically activated in cas − neuroblasts. In addition, the targeted misexpression of Cas in all neuroblast lineages reduces Pdm-1 expression without altering Hb expression. By ensuring correct POU gene expression boundaries, hb and cas maintain temporal subdivisions in the cell-identity circuitry controlling CNS development.

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Neuroblasts: a model for the asymmetric division of stem cells

Cited by 83 publications

References 42 publications

A distinct “side population” of cells with high drug efflux capacity in human tumor cells

A distinct “side population” of cells with high drug efflux capacity in human tumor cells

A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal

Regulation of POU genes by castor andhunchback establishes layered compartments in theDrosophila CNS

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