Chromatin and gene expression changes during female Drosophila germline stem cell development illuminate the biology of highly potent stem cells

Abstract

Highly potent animal stem cells either self renew or launch complex differentiation programs, using mechanisms that are only partly understood. Drosophila female germline stem cells (GSC) perpetuate without change over evolutionary time and generate cystoblast daughters that develop into nurse cells and oocytes. Cystoblasts initiate differentiation by generating a transient syncytial state, the germline cyst, and by increasing pericentromeric H3K9me3 modification, actions likely to suppress transposable element activity. Relatively open GSC chromatin is further restricted by Polycomb repression of testis or somatic cell-expressed genes briefly active in early female germ cells. Subsequently, Neijre/CBP and Myc help upregulate growth and reprogram GSC metabolism by altering mitochondrial transmembrane transport, gluconeogenesis and other processes. In all these respects GSC differentiation resembles development of the totipotent zygote. We propose that the totipotent stem cell state was shaped by the need to resist transposon activity over evolutionary time scales.

Two distinct waves of transcriptome and translatome changes drive Drosophila germline stem cell differentiation

“…Systematic RNA imaging has been used genome-wide to study gene expression patterns in the ovary (Jambor et al, 2015 ), but these scalable methods have not achieved sufficient resolution in the germarium, where stem cell differentiation occurs. Developmental staging, genetic tools and FACS purification have been used to study the transcriptome of GSCs (Kai et al, 2005 ; DeLuca et al, 2020 ), which have been compared to mixed differentiating cysts (Cash and Andrews, 2012 ; Blatt et al, 2021 ) and early follicle stages (Pang et al, 2023 ). Most recently, single-cell RNA sequencing has been performed on whole ovaries by several groups (Jevitt et al, 2020 ; Rust et al, 2020 ; Slaidina et al, 2021 ; Sun et al, 2023 ), identifying mRNA expression signatures of undifferentiated germline cells, immature and mature nurse cells and oocytes, as well as many different somatic cell types of the ovary.…”