Search bioRxiv⌕ Search

Biology subjects

Pang, L.-Y.

Publications and source records attributed to Pang, L.-Y..

2 recordsLinked to original sources

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

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.

developmental biology↗

Differentiating Drosophila female germ cells initiate Polycomb silencing by altering PRC2 sampling

Polycomb silencing represses gene expression and provides a molecular memory of chromatin state that is essential for animal development. We show that Drosophila female germline stem cells (GSCs) provide a powerful system for studying Polycomb silencing and how it is established. GSCs resemble pluripotent mammalian embryonic cells in lacking silenced chromatin, but most GSC daughters, like typical somatic cells, induce Polycomb silencing as they differentiate into nurse cells. Developmentally controlled changes in the levels of two Polycomb repressive complex 2 (PRC2)-interacting proteins, Pcl and Scm, initiate differentiation. In germline stem cells, abundant Pcl inhibits silencing by slowing PRC2 and diverting it from PRE sequences. During differentiation, core PRC2 represses inactive loci while Scm and residual Pcl cooperate to enrich PRC2 and silence traditional Polycomb domains. We propose that PRC2-interacting proteins regulate the transition from a variable to stable transcription state during differentiation by altering the rate that PRC2 samples regulatory sequences.

developmental biology↗