title: Parent stem cells can serve as niches for their daughter cells.
abstract: Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation. Recently, stem cells have been shown to regulate themselves using an autocrine mechanism. 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 cells. Since then, an increasing body of work has focused on defining stem cell niches. 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 cells. Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells . 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.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Pardo-Saganta
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Purushothama Rao
authors.initials: PR
authors.lastname: Tata
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Law
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.|Stem Cell and Regenerative Biology Department, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Borja
authors.initials: B
authors.lastname: Saez
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Ryan Dz-Wei
authors.initials: RD
authors.lastname: Chow
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Mythili
authors.initials: M
authors.lastname: Prabhu
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, Maine 04074, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Departments of Internal Medicine and Pediatrics, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Rajagopal
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D002923:Cilia / Q000378:metabolism; D005260:Female; D000072101:Jagged-2 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D051883:Receptor, Notch2 / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014132:Trachea / Q000166:cytology
chemical_list: C490503:Jag2 protein, mouse; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; C497765:Notch2 protein, mouse; D051883:Receptor, Notch2