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Hof-Michel, S.

Publications and source records attributed to Hof-Michel, S..

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Innate immune signalling drives loser cell elimination during stem cell competition in the Drosophila testis

In the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for the surrounding germline and somatic stem cells. Stem cells of both populations compete for physical retention in the niche, and stem cell clones unable to transduce any one niche signal are rapidly eliminated by differentiation. We have recently mapped the transcriptomes of isolated somatic cyst stem cells and differentiated cyst cells, and found that the stem cells but not their differentiated progeny activate an immune response involving the NF-{kappa}B transcription factor Relish (Rel). Here we show i) that Rel activation is not required for stemness but occurs physiologically in "losers" of stem cell competition, ii) that loss of Rel or the upstream receptor Toll suppresses loser elimination irrespective of how loser fate was induced, and iii) that clonal Rel activation is sufficient for the displacent of neutral or winner cells from the niche, even if the winners otherwise retain stem cell properties. This generalized mechanism for the elimination of "loser" stem cells may mask the compound nature of stem cell behaviour, and instead generate the impression of a binary cell fate decision between stemness and differentiation.

developmental biology

Transcriptome analysis of somatic cell populations in the Drosophila testis links metabolism and stemness

Due to its simple cellular architecture and genetic tractability the fly testis was one of the first model systems in which stem cell - niche interactions were studied at the molecular level. However, to date there is no comprehensive information on the endogenous, cell type specific transcription profiles associated with either stem cell or differentiated states. Focusing on the somatic lineage we have therefore isolated CySCs, differentiated CyCs, hub cells, and stem cell-like tumour cells overexpressing Zfh1, and have mapped their transcriptomes by RNAseq. Here we report i) that the different somatic cell populations show extensive, genome wide differences in transcription levels, in particular associated with energy metabolism and innate immune signalling, ii) that differential activation of multiple signalling pathways renders Zfh1 overexpressing tumour cells unsuitable for use as a stem cell model, and iii) that the transcriptome data could be successfully used for identifying genes with stem cell specific expression patterns and for predicting aspects of stem cell physiology whose relevance for stem cell function could be validated in preliminary experiments. The present data set should therefore facilitate future research on the interaction of stem cells with their niche using the highly successful fly testis model system.

developmental biology