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Cited by 870

The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.

Niche-Independent Symmetrical Self-Renewal of a Mammalian Tissue Stem Cell

Open access
Conti, Luciano, Pollard, Steven M, Gorba, Thorsten, Reitano, Erika, Toselli, Mauro, Biella, Gerardo, Sun, Yirui, Sanzone, Sveva, Ying, Qi-Long, Cattaneo, Elena, Smith, Austin·2005·PLoS Biology
DOI 10.1371/journal.pbio.0030283
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Abstract

Pluripotent mouse embryonic stem (ES) cells multiply in simple monoculture by symmetrical divisions. In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells has proven elusive. Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres. The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated. Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2) and epidermal growth factor (EGF) is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS) cells. NS cells were derived first from mouse ES cells. Neural lineage induction was followed by growth factor addition in basal culture media. In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic. After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain. Colonies generated from single NS cells all produce neurons upon growth factor withdrawal. NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia. Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain. Similar NS cells can be generated from human ES cells and human foetal brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells. The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying differentiation. These homogenous cultures will enable delineation of molecular mechanisms that define a tissue-specific stem cell and allow direct comparison with pluripotent ES cells.

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Crossref · 10.1371/journal.pbio.0030283

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Metadata

Authors
Conti, L., Pollard, S. M., Gorba, T., Reitano, E., Toselli, M., Biella, G., Sun, Y., Sanzone, S., Ying, Q.-L., Cattaneo, E., & Smith, A.
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2005-08-16
Volume
3
Issue
9
Pages
e283
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.0030283
OpenAlex
W2018235103
Cited by
870
References
71
FWCI
13.41
Type
journal article
Language
en
Open access
gold

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