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Stem Cell Reports. 2014 Oct 14;3(4):650-62. doi: 10.1016/j.stemcr.2014.08.008. Epub 2014 Sep 18.

Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis.

Author information

1
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.
2
Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
3
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.
4
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA.
5
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.

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.

PMID:
25358792
PMCID:
PMC4223698
DOI:
10.1016/j.stemcr.2014.08.008
[Indexed for MEDLINE]
Free PMC Article

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