Search all library resources

Molecular logic of adult stem cell self-renewal and the commitment to differentiation in the Drosophila testis stem cell niche [electronic resource]

Adult stem cells both self-renew and give rise to differentiating progeny that maintain and repair tissues throughout an individual's lifetime. Adult stem cells reside in specialized microenvironments, or niches, that regulate stem cell behavior in vivo. The Drosophila testis contains a complex niche that maintains two adult stem cell populations, germline stem cells (GSCs) and somatic cyst stem cells (CySCs), which are directly anchored to a plug of post-mitotic support cells called the hub. A short-range, cytokine-like signal from the hub, the ligand Unpaired (Upd), activates the JAK-STAT pathway in adjacent GSCs and CySCs to promote stem cell maintenance. To map the regulatory circuitry downstream of Upd signaling from the hub, I identified genomic sites of STAT binding in GSCs and CySCs by performing chromatin immunoprecipitation with antibodies against activated STAT, followed by high throughput Solexa sequencing (ChIP-Seq). My analysis suggests that forked regulatory circuits lay downstream of activated STAT in GSCs and CySCs, with different tines containing target gene(s) that regulate unique aspects of stem cell identity and behavior, including sustained receptivity to niche signals, expression of transcriptional regulators required for stem cell fate, and cell-cell communication between germline and soma. Adult stem cell behavior is also influenced by cell-intrinsic factors, including transcription and chromatin remodeling factors, which enable stem cells to interpret and execute appropriate responses to niche signals. I discovered that the transcriptional regulator longitudinals lacking (lola) is required cell autonomously for GSC and CySC maintenance: stem cells homozygous mutant for lola detach from the hub and differentiate. In addition, I found that activity of lola is also required for proper execution of key developmental transitions during germ cell differentiation, including the timely switch from the transit amplification divisions to the spermatocyte growth and gene expression program, and subsequently for the meiosis and spermatid differentiation.