Intestinal stem cells and epithelial-mesenchymal interactions in the crypt and stem cell niche.
The intestinal epithelium contains a rapidly proliferating and perpetually differentiating epithelium. The principal functional unit of the small intestine is the crypt-villus axis. Stem cells located in the crypts of Lieberkühn give rise to proliferating progenitor or transit amplifying cells that differentiate into the 4 major epithelial cell types. The study of adult gastrointestinal tract stem cells has progressed rapidly with the recent discovery of several putative stem cell markers. Substantial evidence suggests 2 populations of stem cells: long-term quiescent (reserved) and actively cycling (primed) stem cells. These cells are in adjoining locations and are presumably maintained by the secretion of specific proteins generated in a unique microenvironment or stem cell niche surrounding each population. The relationship between these 2 populations, as well as the cellular sources and composition of the surrounding environment, remains to be defined, and is an active area of research. In this review, we will outline progress in identifying stem cells and in defining epithelial-mesenchymal interactions in the crypt. We will summarize early advances using stem cells for therapy of gastrointestinal disorders.
Shaker
Anisa
A
Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Rubin
Deborah C
DC
D019485:Bone Morphogenetic Proteins / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D003106:Colon / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000601:surgery; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins
Nat Rev Gastroenterol Hepatol. 2009 Dec;6(12):724-37
19884893
Cell. 2009 Mar 6;136(5):903-12
19269367
Gastroenterology. 2007 Mar;132(3):944-54
17383423
Development. 2005 Jan;132(2):279-89
15590741
Am J Pathol. 2009 Mar;174(3):715-21
19197002
Curr Opin Cell Biol. 2003 Dec;15(6):763-70
14644203
Nat Biotechnol. 2007 Jun;25(6):681-6
17529971
Cell Death Differ. 2010 Jun;17(6):952-61
20019749
Gut. 2006 Jul;55(7):912-4
16766747
Gastroenterology. 2009 Jun;136(7):2195-2203.e1-7
19272384
Nature. 2009 May 14;459(7244):262-5
19329995
Exp Cell Res. 2005 Feb 15;303(2):252-62
15652340
J Nutr. 2004 Nov;134(11):2979-84
15514262
Nature. 2001 Nov 1;414(6859):98-104
11689954
J Clin Invest. 2006 Jun;116(6):1535-46
16710473
Wound Repair Regen. 2005 Jan-Feb;13(1):109-18
15659043
Nat Med. 2009 Jun;15(6):701-6
19398967
Nature. 2009 Jan 29;457(7229):608-11
19092804
Annu Rev Cell Dev Biol. 2005;21:605-31
16212509
Gastroenterology. 2009 Jul;137(1):15-7
19450592
Gastroenterology. 2010 Jun;138(7):2368-77, 2377.e1-4
20206176
Science. 2010 Jan 8;327(5962):210-3
20056890
Leukemia. 2007 Nov;21(11):2271-6
17611560
Nat Genet. 2008 Jul;40(7):818-9
18583974
Am J Anat. 1981 Jan;160(1):93-103
7211719
Methods Enzymol. 2006;419:337-83
17141062
J Clin Invest. 2010 Jun;120(6):2081-93
20458144
Lancet. 2004 May 1;363(9419):1439-41
15121408
Bone Marrow Transplant. 2003 Aug;32(3):337-40
12858208
Nat Genet. 2008 Jul;40(7):915-20
18536716
Nat Genet. 2004 Mar;36(3):277-82
14770182
Bone Marrow Transplant. 2003 Aug;32 Suppl 1:S57-9
12931244
Transplantation. 2003 May 27;75(10):1745-7
12777867
Annu Rev Physiol. 2009;71:241-60
18808327
Int J Exp Pathol. 1997 Aug;78(4):219-43
9505935
Gastroenterology. 2009 Mar;136(3):978-89
19135996
Curr Opin Cell Biol. 2004 Dec;16(6):693-9
15530783
Gastroenterology. 2005 Jun;128(7):1984-95
15940631
Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):266-71
14695885
Science. 2000 Oct 13;290(5490):328-30
11030649
Gastroenterology. 2005 Mar;128(3):552-63
15765390
Genes Dev. 2003 Jul 15;17(14):1709-13
12865297
Gastroenterology. 2009 Jun;136(7):2214-25.e1-3
19505425
Nat Genet. 2004 Oct;36(10):1117-21
15378062
Gastroenterology. 2008 Mar;134(3):849-64
18325394
Nature. 2007 Oct 25;449(7165):1003-7
17934449
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12334-6
11675485
Gastroenterology. 2007 Mar;132(3):1171-3
17383436
Development. 1999 Sep;126(18):4005-15
10457010
Wound Repair Regen. 2009 May-Jun;17(3):296-305
19660036
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15418-23
17881565
Science. 2004 Mar 12;303(5664):1684-6
15017003
Science. 2010 Jan 29;327(5965):542-5
20110496
J Cell Sci. 2002 Jun 1;115(Pt 11):2381-8
12006622
Science. 2009 Jun 26;324(5935):1666-9
19556498
Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1280-8
16439469
Stem Cells. 2009 Oct;27(10):2571-9
19676123