OLFM4は新規腸管ステムのマーカーになりうるや？

２009 May 15 ; ( ) : Gastroenterology van der Flier LG Haegebarth A Stange DE van de Wetering M Clevers H

OLFM4２ is a Robust Marker for Stem Cells in Human Intestine and Marks a Subset of Colorectal Cancer Cells.

Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalaan 8, 3584 CT Utrecht, The Netherlands.

The epithelium of the small intestine and colon is the most rapidly self-renewing tissue of mammals. Proliferative cells are confined to crypts, while differentiated cell types predominantly occupy the villi in the small intestine and the surface epithelium in the colon. We recently demonstrated the existence of a long-lived pool of cycling stem cells defined by Lgr5expression. These cells are intermingled with post-mitotic Paneth cells at crypt bottoms in the small intestine. In the colon, they reside at crypt bottoms and are intermingled with goblet cells. While knock-in alleles of Lgr5 have been instrumental in defining these cells, Lgr5 mRNA or protein levels are too low to serve as faithful markers. Olfactomedin-4 (Olfm4)has emerged from a gene signature for these Lgr5 stem cells as a robust marker for murine small intestinal stem cells. Here we show that OLFM4is highly expressed in crypt base columnar cells in human small intestine and colon. Moreover, OLFM4is expressed in cells within adenocarcinomas of the colon. We propose that OLFM4 can serve as a useful marker for Lgr5-type stem cells in human small intestine and colon.

OLFM4は新規腸管ステムのマーカーになりうるや？
Clevers Hの新作である。まだ最終草稿の段階でon line化されている。Lgr5があまりに使いにくいマーカーなので、とうことで同様の動きをするより発現量の高い遺伝子として候補に挙げられた。正直このレベルでよくGastroenterorlogyが採用したと思うくらいデータが足りない。

ただしこの論文、一つ前のcellの論文に準拠しているようだ。

2009 Mar 6 ; 136 ( 5 ) : 903-12 Cell

van der Flier LG van Gijn ME Hatzis P Kujala P Haegebarth A Stange DE Begthel H van den Born M Guryev V Oving I van Es JH Barker N Peters PJ van de Wetering M Clevers H

Transcription factor achaete scute-like 2 controls intestinal stem cell fate.
Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalaan, The Netherlands.

The small intestinal epithelium is the most rapidly self-renewing tissue of mammals. Proliferative cells are confined to crypts, while differentiated cell types predominantly occupy the villi. We recently demonstrated the existence of a long-lived pool of cycling stem cells defined by Lgr5 expression and intermingled with post-mitotic Paneth cells at crypt bottoms. We have now determined a gene signature for these Lgr5 stem cells. One of the genes within this stem cell signature is the Wnt target Achaete scute-like 2 (Ascl2). Transgenic expression of the Ascl2 transcription factor throughout the intestinal epithelium induces crypt hyperplasia and ectopic crypts on villi. Induced deletion of the Ascl2 gene in adult small intestine leads to disappearance of the Lgr5 stem cells within days. The combined results from these gain- and loss-of-function experiments imply that Ascl2 controls intestinal stem cell fate.


こちらの論文をよむと納得いくのかもしれないと思う。納得できたとして、OLFM4２ の抗体がavailableだといいが。