Drosophila Perlecan Regulates Intestinal Stem Cell Activity via Cell-Matrix Attachment

Stem cells require specialized local microenvironments, termed niches, for normal retention, proliferation, and multipotency. Niches are composed of cells together with their associated extracellular matrix (ECM). Currently, the roles of ECM in regulating niche functions are poorly understood. Here, we demonstrate that Perlecan (Pcan), a highly conserved ECM component, controls intestinal stem cell (ISC) activities and ISC-ECM attachment in Drosophila adult posterior midgut. Loss of Pcan from ISCs, but not other surrounding cells, causes ISCs to detach from underlying ECM, lose their identity, and fail to proliferate. These defects are not a result of a loss of epidermal growth factor receptor (EGFR) or Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity but partially depend on integrin signaling activity. We propose that Pcan secreted by ISCs confers niche properties to the adjacent ECM that is required for ISC maintenance of stem cell identity, activity, and anchorage to the niche. [Display omitted] •Pcan regulates ISC activity and ISC-ECM attachment in Drosophila adult midgut•Loss of Pcan from ISC, but not other surrounding cells, causes the ISC defects•Functions of Pcan are independent of EGFR and JAK/STAT signaling pathways•ISC secrets Pcan to establish a niche for itself Stem cells require niches for normal activities. Currently, the roles of extracellular matrix (ECM) in regulating niche functions and stem cell activities are poorly understood. Here, Lin and colleagues demonstrate that Perlecan (Pcan) controls intestinal stem cell activities and stem cell-ECM attachment in Drosophila adult posterior midgut. Our results suggest that ISC secrets Pcan to form an activated ECM and, therefore, establish a niche for itself.