A Transient Niche Regulates the Specification of Drosophila Intestinal Stem Cells

Abstract

Stem cell niches are locations where stem cells reside and self-renew. Although studies have shown how niches maintain stem cell fate during tissue homeostasis, less is known about their roles in establishing stem cells. The adult Drosophila midgut is maintained by intestinal stem cells (ISCs); however, how they are established is unknown. Here, we show that an ISC progenitor generates a niche cell via Notch signaling. This niche uses the bone morphogenetic protein 2/4 homolog, decapentaplegic, to allow progenitors to divide in an undifferentiated state and subsequently breaks down and dies, resulting in the specification of ISCs in the adult midgut. Our results demonstrate a paradigm for stem cell-niche biology, where progenitors generate transient niches that determine stem cell fate and may give insights into stem cell specification in other tissues.Intercellular factors regulate stem cell proliferation and maintenance in stem cell niches in the Drosophila ovary (1) and testis (2,3), as well as in mammalian systems, such as the hematopoietic system (4-6), skin (7), and neural cells (8). These niches, which are generally fixed stromal locations, signal to prevent stem cell differentiation (9,10). However, even though the role of niches in the maintenance of tissue homeostasis has been well examined, relatively little is known about their function in establishing stem cell lineages during organogenesis.The lineage of intestinal stem cells (ISCs) in the adult Drosophila midgut (11,12) can be tracked to determine how progenitors establish different intestinal cells during development. Adult midgut progenitors (AMPs) from the three larval stages generate all epithelial cells in the adult midgut, including ISCs, enterocytes, and enteroendocrine cells (table S1) (13,14). In the first two instars (L1 and L2), AMPs proliferate and disperse throughout the midgut. Dispersal stops by the third instar (L3), when AMPs proliferate and form clusters known as midgut imaginal islands. During metamorphosis, when the larval gut histolyses, the islands merge and generate the adult midgut epithelium, including ISCs, enterocytes, and

Developmental control of the DNA replication and transcription programs

“…Midgut-specific transcripts were enriched in GO categories such as larval or pupal organ development and morphogenesis, metamorphosis, and imaginal disc development. The latter categories likely reflect the developmental events as the larval midgut is degraded and the adult midgut rebuilt from imaginal islands in the midgut (Skaer 1993;Jiang et al 2009;Mathur et al 2010). Salivary gland-specific transcripts were enriched in GO processes such as puparial adhesion, molting cycle, and DNA replication, again consistent with tissue function (Supplemental Tables 3-5).…”

“…In contrast, the larval midgut is responsible for nutrient uptake and is composed of large polytene cells and diploid imaginal cells (Skaer 1993). The two cell types of the larval midgut respond to the steroid hormone ecdysone in different ways during metamorphosis, as the diploid cells produce the adult midgut but the larval midgut is histolyzed (Li and White 2003;Jiang et al 2009;Mathur et al 2010). Polytene structures of both larval midgut and fat body chromosomes show banding patterns similar to those of the larval salivary gland (Hochstrasser 1987).…”

Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

“…Larval AMPs undergo a series of cell divisions, which are regulated through cell autonomous activation of the EGFR/MAPK signalling by EGF ligands emanating from the visceral muscle and AMPs themselves ). Additionally, a transient Dpp/BMP niche provided by peripheral cells (PC) enwrapping AMPs is required to allow AMP proliferation while preventing their differentiation (Mathur et al, 2010). As the animal enters metamorphosis, the larval midgut degenerates except for clusters of AMPs, which merge throughout the pupal stage to generate the adult midgut epithelium (Mathur et al, 2010) (Nakagoshi, 2005) (Takashima and Hartenstein, 2012) (Micchelli, 2012) .…”

Simultaneous control of stemness and differentiation by the transcription factor Escargot in adult stem cells: How can we tease them apart?

“…In contrast, we utilized a relatively weaker Geneswitch driver, 5961-gal4 GS , [36][37][38] which would knock-down Esg more gradually and allow for a window during which ISC/EBs express less Esg and yet maintain stem cell identity.…”