Stem cells: Chromatin remodelling finds its niche

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In Drosophila, two chromatin-remodeling factors of the SWI/SNF family — imitation SWI (ISWI) and Domino (DOM) — prevent stem cells from differentiating.

A key feature of stem cells is their capacity for self-renewal — an ability that relies on signals from the surrounding stem-cell niche. But how do these signals stop stem cells from becoming differentiated? Studies in the fruitfly ovary show that chromatin-remodelling proteins have an essential role.

The possibility that chromatin-remodelling proteins regulate access to DNA to prevent stem-cell differentiation is an attractive theory that has already been proposed for some types of stem cell. Xi and Xie tested whether this applies in the ovary of Drosophila melanogaster, which contains both germline stem cells (GSCs) and somatic stem cells (SSCs). The signals provided by the stem-cell niche are well-characterized in this system, allowing the mechanisms that translate these signals at the level of gene expression to be explored.

The authors looked at the roles of two chromatin-remodelling factors of the SWI/SNF family — imitation SWI (ISWI) and Domino (DOM) — by generating marked clones of GSCs and SSCs that are mutant for either iswi or dom. Loss of ISWI function in GSCs had a dramatic effect — after 2 weeks, almost all iswi mutant cells had been lost, compared with just 35% of wild-type GSCs. A similar requirement for DOM was shown for SSCs.

What causes the loss of stem cells when these remodelling factors are absent? The authors ruled out effects on survival and cell division, and concluded that ISWI and DOM are needed for self-renewal, to prevent GSCs and SSCs from differentiating.

Finally, Xi and Xie showed that signals from the stem-cell niche are responsible for controlling self-renewal through their effects on chromatin-remodelling proteins. In GSCs, bone morphogenetic protein (BMP) signals are required for self-renewal through a pathway that involves alterations in gene expression. In iswi mutant cells, however, BMP signalling was no longer able to bring about the necessary changes in transcription.

As well as showing how signals from the stem-cell niche prevent differentiation, this study also demonstrates that different chromatin-remodelling proteins are required for self-renewal in distinct stem-cell types; both findings should prompt similar investigations in other systems.

Louisa Flintoft

References

Xi, R. & Xie, T. Stem cell self-renewal controlled by chromatin remodeling factors. Science 310, 1487–1489 (2005) | Article | PubMed |