Biology subjects

Hof-Michel, S.

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

3 recordsLinked to original sources

bioRxiv2021

Cell cycle exit and stem cell differentiation are coupled through regulation of mitochondrial activity in the Drosophila testis

Stem cells maintain tissue homeostasis by proliferating to replace cells lost to damage or natural turnover. Whereas stem and progenitor cells proliferate, fully differentiated cells exit the cell cycle. How cell identity and cell cycle state are coordinated during this process is still poorly understood. The Drosophila testis niche supports germline stem cells and somatic cyst stem cells (CySCs), which are the only proliferating somatic cells in the testis. CySCs give rise to post-mitotic cyst cells and therefore provide a tractable model to ask how stem cell identity is linked to proliferation. We show that the G1/S cyclin, Cyclin E, is required for CySC self-renewal; however, its canonical transcriptional regulator, a complex of the E2f1 and Dp transcription factors is dispensable for self-renewal and cell cycle progression. Nevertheless, we demonstrate that E2f1/Dp activity must be silenced to allow CySCs to differentiate. We show that E2f1/Dp activity inhibits the expression of genes important for mitochondrial activity. Furthermore, promoting mitochondrial activity or biogenesis is sufficient to rescue the differentiation of CySCs with ectopic E2f1/Dp activity but not their exit from the cell cycle. Our findings together indicate that E2f1/Dp coordinates cell cycle progression with stem cell identity by regulating the metabolic state of CySCs.

developmental biology↗

bioRxiv2020

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↗

bioRxiv2020

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↗