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  • Review Article
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The stem-cell niche theory: lessons from flies

Nature Reviews Genetics volume 3, pages 931–940 (2002)Cite this article

Key Points

  • A stem-cell niche is a restricted locale in an organ that supports the self-renewing division of stem cells and so prevents them from differentiating.

  • Cap and terminal filament cells and hub cells constitute the stem-cell niche in the fly ovary and testis, respectively.

  • Both ovarian and testicular stem-cell niches are dual-functional niches that emanate signals that are essential for the maintenance of both germline and somatic stem cells.

  • The ovarian niche generates several signalling pathways, including the Decapentaplegic (Dpp) and female sterile (1) Yb (Yb)/Piwi/Hedgehog (Hh)-mediated pathways, which act in parallel to maintain germline stem cells.

  • The Yb/Piwi/Hh-mediated pathway bifurcates downstream of Yb, with the Piwi and Hh branches mainly responsible for the maintenance of germline and somatic stem cells, respectively.

  • Cell adhesions through adherens junctions anchor both germline and somatic stem cells to the niche.

  • The testicular niche generates the Unpaired ligand that is essential for the self-renewal of both germline and somatic stem cells.

  • In contrast to its oogenic function, the Dpp pathway functions to restrict the proliferation of gonialblasts and spermatogonia in males. Epidermal growth factor receptor and Raf also have this function.

  • The organization and signalling pathways of the fly niches provide guiding principles for studying stem-cell niches in mammalian systems.

Abstract

Stem cells are characterized by their ability to self-renew and to produce numerous differentiated cell types, and are directly responsible for generating and maintaining tissues and organs. This property has long been attributed to the instructive signals that stem cells receive from their microenvironment — the so-called 'stem-cell niche'. Studies of stem cells in the Drosophila gonad have yielded much exciting insight into the structure of the niche and the signalling pathways that it produces to regulate the self-renewal of stem cells. These findings are illuminating our understanding of the self-renewing mechanisms of tissue stem cells in general.

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Figure 1: Somatic signalling pathways in the Drosophila ovarian stem-cell niche.
Figure 2: Germline and somatic stem cells and their niches in the Drosophila testis.
Figure 3: Somatic signalling pathways in the Drosophila testicular stem-cell niche.

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Acknowledgements

I thank P. Bhattacharaya, M. Goddeeris, S. Grivna, M. Rivas, A. Szakmary and Z. Wang for their critical reading of the manuscript at extremely short notice. I also thank three anonymous reviewers for their comments. The writing of this review and the germline stem-cell research in my laboratory are supported by grants from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Cell Biology, Box 3709, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Haifan Lin

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DATABASES

LocusLink

arm

Bmp8b

Ci

c-Kit

DE-cadherin

dpp

Egfr

en

Erk

fs(1)Yb

hh

Hop

Jak

Mad

Med

Miwi

Notch

piwi

ptc

punt

raf

Shh

shn

Smo

Stat

Steel

Upd

Wnt

zpg

Flybase

innexin 4

FURTHER INFORMATION

Haifan Lin's laboratory

Glossary

TRANS-DIFFERENTIATION

The process by which stem or progenitor cells of one tissue give rise to the cell types of another tissue.

STROMAL CELL

A connective tissue cell such as a fibroblast. In the stem-cell literature, this term often refers specifically to the connective cells that provide immediate support to a particular cell type.

PAPILLA CELL

A stromal cell at the edge of the dermis that is in contact with the epidermis.

CRYPT

The inpocketings on the lumenal surface of the small intestine.

MOSAIC ANALYSIS

(also known as clonal analysis). The use of genetic or surgical operations to generate a genetically mosaic organism to examine the cell-autonomous (effect restricted to the cell in which it is expressed) versus cell-non-autonomous nature of a gene or developmental process.

ADHERENS JUNCTION

A region of cell–cell adhesion that contains cadherin, which forms cell–cell junctions, and catenins, which anchor the actin skeleton to the plasma membrane.

GERMARIUM

The apical, corn-shaped part of the insect ovariole (the functional unit of the insect ovary) that contains both germline and follicle stem cells and is responsible for the continuous production of new egg chambers.

SIGNAL PEPTIDE

(or signal sequence). A short, 15–30-amino-acid sequence on a newly translated polypeptide that functions as a signal for its secretion from the cell. The signal peptide is removed as the protein is secreted.

GAP JUNCTION

A type of junction between two cells through which ions and small molecules can pass.

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Lin, H. The stem-cell niche theory: lessons from flies. Nat Rev Genet 3, 931–940 (2002). https://doi.org/10.1038/nrg952

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