Identification of a putative intestinal stem cell and early lineage marker; musashi-1

Potten, Christopher S; Booth, Catherine; Tudor, Gregory; Booth, Dawn; Brady, Gerard; Hurley, Patricia; Ashton, Gary; Clarke, Robert B.; Sakakibara, Shin-ichi; Okano, Hideyuki

doi:10.1046/j.1432-0436.2003.700603.x

Cited by 441 publications

(418 citation statements)

References 34 publications

(69 reference statements)

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“…We first detected GFP + cells 3 d after completion of pIpC treatment (day 3). Costaining with the stem cell marker Musashi1 (referred to hereafter as 'Musashi') 24 confirmed that recombination had occurred in ISCs (Fig. 1b).…”

Section: Induced Inactivation Of Pten Leads To Intestinal Polyposismentioning

confidence: 76%

“…1 online). Rat monoclonal anti-Musashi yielded a slightly broader pattern of signal but had a similar distribution of strongly positive cells 24 ( Supplementary Fig. 2 online).…”

Section: Musashi + Stem and Progenitor Cells Initiate Polyp Formationmentioning

confidence: 94%

“…9) and that PTEN loss results in polyposis raise the possibility that PTEN-deficient ISCs are responsible for polyp formation. To test this hypothesis, we tracked ISCs using the marker Musashi 24 . In normal intestinal crypts, we detected two classes of Musashi + cells by a polyclonal antibody to Musashi (anti-Musashi) (Chemicon; cat.…”

Section: Musashi + Stem and Progenitor Cells Initiate Polyp Formationmentioning

confidence: 99%

“…Similarly, we propose that aberrantly located Musashi + cells direct the de novo budding morphogenesis of crypt-like structures from existing villi or crypts. This budding process will probably share some of the molecular and cellular characteristics of the initial formation of crypts during intestinal development, in which Musashi + cells demonstrate a similar distribution 24,42 . …”

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PTEN-deficient intestinal stem cells initiate intestinal polyposis

et al. 2007

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Intestinal polyposis, a precancerous neoplasia, results primarily from an abnormal increase in the number of crypts, which contain intestinal stem cells (ISCs). In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement. Using this model, we have established the relationship between stem cells and polyp and tumor formation. PTEN helps govern the proliferation rate and number of ISCs and loss of PTEN results in an excess of ISCs. In PTENdeficient mice, excess ISCs initiate de novo crypt formation and crypt fission, recapitulating crypt production in fetal and neonatal intestine. The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector β-catenin. Akt phosphorylates β-catenin at Ser552, resulting in a nuclear-localized form in ISCs. Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of β-catenin. Accession codes. Gene Expression Omnibus (GEO): GSE6078.URLs. GEO: http://www.ncbi.nlm.nih.gov/projects/geo/.Supplementary information is available on the Nature Genetics website. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. HHS Public AccessAuthor manuscript Nat Genet. Author manuscript; available in PMC 2015 December 16. Published in final edited form as:Nat Genet. 2007 February ; 39(2): 189-198. doi:10.1038/ng1928. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe failure of most current therapies to cure cancer has led to the hypothesis that treatments targeted at malignant proliferation spare a more slowly cycling 'cancer stem cell' population that has the ability to regenerate the tumor 1 . Recently, cancer stem cells have been identified and shown to seed tumors upon transplantation into a secondary host [2][3][4] . However, little is known about the process by which mutation(s) in a stem cell result in primary tumor initiation.Although there are many 'causes' of intestinal cancer, it is well established that almost all cases begin with the development of benign polyps, mainly involving benign neoplastic proliferation of epithelium. The epithelium of the small intestine is composed of a proliferation compartment (crypt) and a differentiation compartment in the villus (Fig. 1a). ISCs, located near the crypt base and above Paneth cells 5,6 , give rise to enterocytes, goblet cells, enteroendocrine cells and Paneth cells [6][7][8] . Intestinal polyposis features a substantial increase in the number of crypts (crypt expansion) and a reduction in epithelial cell differentiation 6,7,9,10 . A key question 7,9,11 is whether stem cells are involved in the abnormal crypt expansion during polyp initiation.Studies of human hereditary intestinal polyposis syndromes (which typically, but not uniformly, predispose affected individuals to gastrointes...

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Section: Induced Inactivation Of Pten Leads To Intestinal Polyposismentioning

confidence: 76%

“…1 online). Rat monoclonal anti-Musashi yielded a slightly broader pattern of signal but had a similar distribution of strongly positive cells 24 ( Supplementary Fig. 2 online).…”

Section: Musashi + Stem and Progenitor Cells Initiate Polyp Formationmentioning

confidence: 94%

Section: Musashi + Stem and Progenitor Cells Initiate Polyp Formationmentioning

confidence: 99%

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confidence: 98%

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PTEN-deficient intestinal stem cells initiate intestinal polyposis

et al. 2007

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“…Msi-1 has also been advocated as a stem cell marker in the gut; in the rat stomach Msi-1-expressing cells are located just beneath the foveolar region (the putative niche), although there was some expression in parietal cells [66]. Msi-1 also marks putative stem cells in the mouse intestine [67]; interestingly, in the small intestine, not only were the cells at cell positions 4-5 immunolabelled, but also very slender cells intermingled with Paneth cells -the socalled 'crypt base columnar cells', now known to express Lgr5 and capable of multilineage differentiation [4]. Although Msi-1 has not been considered as a marker of colorectal cancer stem cells, a quite remarkable suppression of tumour growth occurred when siRNA-knockdown of Msi-1 was achieved in a xenografted colorectal cancer cell line [68].…”

Section: Markers Related To Stem Cell Functionmentioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Culture of Specific Cell Types

Freshney

2005

Culture of Animal Cells

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Identification of a putative intestinal stem cell and early lineage marker; musashi-1

Cited by 441 publications

References 34 publications

PTEN-deficient intestinal stem cells initiate intestinal polyposis

PTEN-deficient intestinal stem cells initiate intestinal polyposis

Attributes of adult stem cells

Culture of Specific Cell Types

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