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.

In an earlier paper (Pérez-Montero et al., 2013), we reported that the embryonic linker histone of Drosophila dBigH1 was essential for early Drosophila embryogenesis since embryos homozygous for the bigH1 100 mutation showed strong defects and did not survive beyond zygotic genome activation (ZGA) at cellularization. Recent results challenge these observations since null bigH1 mutations generated by CRISPR/Cas9 methodology turn out to be homozygous viable, as reported in Li et al. (2019) and here. In this regard, Li et al. described a novel mechanism by which lack of dBigH1 is compensated by the early expression of maternal dH1. Here, we confirm this observation and show that such compensatory mechanism is not activated in bigH1 100 embryos.

Linker histones H1 are essential chromatin components that exist as multiple developmentally regulated variants. In metazoans, specific H1s are expressed during germline development in a tightly regulated manner. However, the mechanisms governing their stage-dependent expression are poorly understood. Here, we address this question in Drosophila , which encodes for a single germline-specific dBigH1 linker histone. We show that during female germline lineage differentiation, dBigH1 is expressed in germ stem cells and cystoblasts, becomes silenced during transit-amplifying (TA) cystocytes divisions to resume expression after proliferation stops and differentiation starts, when it progressively accumulates in the oocyte. We find that dBigH1 silencing during TA divisions is post-transcriptional and depends on the tumour suppressor Brain tumour (Brat), an essential RNA-binding protein that regulates mRNA translation and stability. Like other oocyte-specific variants, dBigH1 is maternally expressed during early embryogenesis until it is replaced by somatic dH1 at the maternal-to-zygotic transition (MZT). Brat also mediates dBigH1 silencing at MZT. Finally, we discuss the situation in testes, where Brat is not expressed, but dBigH1 is translationally silenced too.