title: Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis.
abstract: The mammalian kidney is a complex organ consisting of multiple cell types. We previously showed that the Six2-expressing cap mesenchyme is a multipotent self-renewing progenitor population for the main body of the nephron, the basic functional unit of the kidney. However, the cellular mechanisms establishing stromal tissues are less clear. We demonstrate that the Foxd1-expressing cortical stroma represents a distinct multipotent self-renewing progenitor population that gives rise to stromal tissues of the interstitium, mesangium, and pericytes throughout kidney organogenesis. Fate map analysis of Foxd1-expressing cells demonstrates that a small subset of these cells contributes to Six2-expressing cells at the early stage of kidney outgrowth. Thereafter, there appears to be a strict nephron and stromal lineage boundary derived from Six2-expressing and Foxd1-expressing cell types, respectively. Taken together, our observations suggest that distinct multipotent self-renewing progenitor populations coordinate cellular differentiation of the nephron epithelium and renal stroma during mammalian kidney organogenesis.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA; Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA. Electronic address: akiok@uw.edu.
authors.forename: Akio
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Mugford
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, W. M. Keck School of Medicine, University of Southern California, Los Angeles, 1425 San Pablo Street, Los Angeles, CA 90089, USA.
authors.forename: A Michaela
authors.initials: AM
authors.lastname: Krautzberger
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Naiman
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA; Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, W. M. Keck School of Medicine, University of Southern California, Los Angeles, 1425 San Pablo Street, Los Angeles, CA 90089, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse; D018398:Homeodomain Proteins; C497420:Six2 protein, mouse; D014157:Transcription Factors