Decoding the Regulatory Logic of the Drosophila Male Stem Cell System

Abstract

The niche critically controls stem cell behavior, but its regulatory input at the whole-genome level is poorly understood. We elucidated transcriptional programs of the somatic and germline lineages in the Drosophila testis and genome-wide binding profiles of Zfh-1 and Abd-A expressed in somatic support cells and crucial for fate acquisition of both cell lineages. We identified key roles of nucleoporins and V-ATPase proton pumps and demonstrate their importance in controlling germline development from the support side. To make our dataset publicly available, we generated an interactive analysis tool, which uncovered conserved core genes of adult stem cells across species boundaries. We tested the functional relevance of these genes in the Drosophila testis and intestine and found a high frequency of stem cell defects. In summary, our dataset and interactive platform represent versatile tools for identifying gene networks active in diverse stem cell types.

Nuclear export in somatic cyst cells controls cyst cell-germline coordination and germline differentiation in theDrosophilatestis

“…In a previous study we identified nucleoporins as important regulators of cyst cell function and cyst cell-germline coordination (Tamirisa et al, 2018). In this study, we go one step further and highlight the critical function of three new nucleoporins in Drosophila testis cyst cells, the central channel FG-rich Nup62, the cytoplasmic ring proteins Nup214 and Nup88, and of the unique Drosophila Exportin encoded by the embargoed (emb) gene.…”

“…Loss of Nup98-96 leads to dramatic cell autonomous effects in Drosophila male germ cells, since germ cells differentiate prematurely to spermatocytes at the 2-, 4-, and 8-germ cell cysts stage (Parrott et al, 2011). Moreover, loss of nup205, nup93-1, nup358, nup44A in Drosophila testis cyst cells leads to an overproliferation of early germ cells (Tamirisa et al, 2018). Finally, LamDm0 acts downstream of the EGFR pathway and together with the nuclear basket Nup153 and Mtor regulate nuclear retention of the phosphorylated MAPK dpERK (Chen et al, 2013).…”

“…Previous studies have shown that overproliferation of early germ cells results non-cell autonomously when cyst cell function is compromised by forced activation of the pro-apoptotic gene grim, by impaired germ cell encapsulation e.g. upon loss of the actin polymerization protein Profilin chic or when cyst cells cannot instruct germ cell differentiation due to signaling loss (Ayyub et al, 2015;Dominado et al, 2016;Gonzalez et al, 2015;Li et al, 2003;Qian et al, 2015;Saito et al, 2009;Shields et al, 2014;Tamirisa et al, 2018). Consistently, we found that the viability of the cyst cells was largely restored when apoptosis was prevented in nup62, emb, nup214 and nup88 cyst cells knockdowns in L3 and adult testes by co-expression of the antiapoptotic baculovirus protein p35 (Hay et al, 1994) (Fig.4 and S4).…”

“…The massive overproliferation of the germline, resembling early-stage germ cell tumors in the absence of germline differentiation, is not only manifested when cyst cells are dying (Lim and Fuller, 2012). It also appears, as a cell non-autonomous effect, whenever cyst cells are unable to encapsulate properly the germline or whenever signals normally emanating from cyst cells are lost, resulting in impaired germline differentiation (Ayyub et al, 2015;Dominado et al, 2016;Gonzalez et al, 2015;Li et al, 2003;Qian et al, 2015;Saito et al, 2009;Shields et al, 2014;Tamirisa et al, 2018). Knockdown of the Drosophila homologue of Profilin, encoded by the chickadee (chic) gene, in the cyst cells impairs germ cell enclosure, restricts TA spermatogonial divisions and results in early germ cell overproliferation, while cyst cells are progressively lost over time (Shields et al, 2014).…”

Targeted molecular profiling of rare cell populations identifies olfactory sensory neuron fate and wiring determinants

“…The selectivity of expression of Dam:PolII or Dam avoids the requirement for cell isolation prior to genomic DNA extraction. Previous applications of TaDa in Drosophila have profiled relatively abundant cell populations in central brain tissue, the intestine or the male germline 14, [17][18][19] . Although OSN classes can be effectively labeled using transgenes containing promoters for the corresponding receptor genes, it was unclear whether TaDa would be sufficiently sensitive to measure transcriptional activity from an individual population of sensory neurons within the antenna.…”