Histone H1 defect in escort cells triggers germline tumor in Drosophila ovary

Abstract

Drosophila ovary is recognized as one of the best model systems to study stem cell biology in vivo. We had previously identified an autonomous role of the histone H1 in germline stem cell (GSC) maintenance. Here, we found that histone H1 depletion in escort cells (ECs) resulted in an increase of spectrosome-containing cells (SCCs), an ovary tumor-like phenotype. Further analysis showed that the Dpp pathway is excessively activated in these SCC cells, while the expression of bam is attenuated. In the H1-depleted ECs, both transposon activity and DNA damage had increased dramatically, followed by EC apoptosis, which is consistent with the role of H1 in other somatic cells. Surprisingly, H1-depleted ECs acquired cap cell characteristics including dpp expression, and the resulting abnormal Dpp level inhibits SCC further differentiation. Most interestingly, double knockdown of H1 and dpp in ECs can reduce the number of SCCs to the normal level, indicating that the additional Dpp secreted by ECs contributes to the germline tumor. Taken together, our findings indicate that histone H1 is an important epigenetic factor in controlling EC characteristics and a key suppressor of germline tumor.

Traffic jam regulates the function of the ovarian germline stem cell progeny differentiation niche during pre-adult stage in Drosophila

“…Previous studies have also shown that UGC accumulation caused by extrinsic EC defects is always coupled with severe loss of ECs 10,24–26,28,46 , indicating that a certain number of EC is required for non-cell autonomous control of germline differentiation. To determine whether Tj controls EC number, the enhancer trap line PZ1444 52,53 , which labels both CpCs and ECs, was used to directly quantify the EC number in germaria.…”

“…What motivates the ectopic BMP activity outside the GSC niche? Several correlative studies suggest complex mechanisms, in which a population of ECs is capable of expressing Dpp as well as other niche cell markers under certain conditions 20,21,25,26,28 . Together, they reveal that tightly regulated dpp transcription is required to maintain homeostasis of adult ovaries.…”

“…Interestingly, Wnt signaling in ECs regulates the Tkv expression without repressing Dally and Dpp 17 . On the other hand, Lsd1 20,21 , Piwi 22,23 , COP9/Hh 24,25 and H1 26 have been reported to control GSC progeny differentiation through repressing Dpp expression in ECs. Moreover, Rho1 10 and Bre1/Set1 27 function in ECs to inhibit both Dpp and Dally production.…”

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

“…Further analysis is needed to investigate whether these proteins actually bind to endogenous TSC22D1 family proteins under intracellular physiological conditions and to examine functional interactions, but it was clear that histone H1 binds to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in cells. Histone H1 is a linker histone and its overexpression induces an abnormal nuclear morphology and chromatin structure, which positively and negatively regulates transcription in vitro (Figure 8A) [20,[40][41][42][43]. We propose the possible mechanisms between the TSC22D1 family and histone H1 (Figure 8A).…”

MiMIC analysis reveals an isoform specific role forDrosophilaMusashi in follicle stem cell maintenance and escort cell function

“…The cystoblast continues to divide, with the end result being the production of 16-cell cysts in region 2b of the germarium (Spradling, 1993). Somatic ECs are typically quiescent and support the developing germline, with tight association of ECs with the germline being necessary for germline development (Banisch, Maimon, Dadosh, & Gilboa, 2017; Kirilly, Wang, & Xie, 2011; Maimon, Popliker, & Gilboa, 2014; Yang et al, 2017). ECs are highly dynamic in nature and protrude within the packed germarium to invade and engulf the germline (Banisch et al, 2017).…”