Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance1,2, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation3,4,5,6. Recently, stem cells have been shown to regulate themselves using an autocrine mechanism7. The existence of a ‘stem cell niche’ was first postulated by Schofield in 1978 to define local environments necessary for the maintenance of haematopoietic stem cells1. Since then, an increasing body of work has focused on defining stem cell niches1,2,3,4,5,6. Yet little is known about how progenitor cell and differentiated cell numbers and proportions are maintained. In the airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory cells and ciliated cells8,9. Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells9,10 . Here we describe a mode of cell regulation in which adult mammalian stem/progenitor cells relay a forward signal to their own progeny. Surprisingly, this forward signal is shown to be necessary for daughter cell maintenance. Using a combination of cell ablation, lineage tracing and signalling pathway modulation, we show that airway basal stem/progenitor cells continuously supply a Notch ligand to their daughter secretory cells. Without these forward signals, the secretory progenitor cell pool fails to be maintained and secretory cells execute a terminal differentiation program and convert into ciliated cells. Thus, a parent stem/progenitor cell can serve as a functional daughter cell niche.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
We thank A. Glick for providing the CK5rtTA mice, B. Hogan for providing CK5creER and SCGB1A1creER mice and Y.-Y. Kong for sharing the Mib1 floxed mice. B. Z. Stanger provided the RBPjk floxed mice and shared protocols for the immunohistochemical detection of Notch components. We also thank B. Stripp for providing the goat anti-SCGB1A1 antibody. We wish to extend our thanks to all of the members of the Rajagopal laboratory and the HSCI flow cytometry core facility. This research was supported by the New York Stem Cell Foundation (J.R. is a New York Stem Cell Foundation-Robertson Investigator), by a National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty (P30) award (5P30HL101287-02), an RO1 (RO1HL118185) from NIH-NHLBI (to J.R.) and a Harvard Stem Cell Institute (HSCI) Junior Investigator Grant (to J.R.). J.R. is also the Maroni Research Scholar at Massachusetts General Hospital.