Identification of a putative intestinal stem cell and early lineage marker; musashi-1.
There are few reliable markers for adult stem cells and none for those of the intestinal epithelium. Previously, indirect experimental approaches have predicted stem cell position and numbers. The Musashi-1 (Msi-1) gene encodes an RNA binding protein associated with asymmetric divisions in neural progenitor cells. Two-day-old, adult, and 4.5 h, 1-, 2-, 4- and 12-day post-irradiation samples of BDF1 mouse small intestine, together with some samples of mouse colon were stained with a rat monoclonal antibody to Musashi-1 (14 H-1). Min ( + / - ) mice with small intestinal adenomas of varying sizes were also analysed. Samples of human small and large bowel were also studied but the antibody staining was weak. Musashi-1 expression was observed using immunohistochemistry in neonatal, adult, and regenerating crypts with a staining pattern consistent with the predicted number and distribution of early lineage cells including the functional stem cells in these situations. Early dysplastic crypts and adenomas were also strongly Musashi-1 positive. In situ hybridization studies showed similar expression patterns for the Musashi mRNA and real-time quantitative RT-PCR showed dramatically more Msi-1 mRNA expression in Min tumours compared with adjacent normal tissue. These observations suggest that Musashi-1 is a marker of stem and early lineage progenitor cells in murine intestinal tissue.
Potten
Christopher S
CS
Epithelial Biology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. c.potten@epistem.co.uk
Booth
Catherine
C
Tudor
Gregory L
GL
Booth
Dawn
D
Brady
Gerard
G
Hurley
Patricia
P
Ashton
Gary
G
Clarke
Robert
R
Sakakibara
Shin-ichi
S
Okano
Hideyuki
H
D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D019070:Cell Lineage; D002648:Child; D005720:Gamma Rays; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D015415:Biomarkers; C491297:MSI1 protein, human; C491296:Msi1 protein, rat; C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins