Transcription factor Oct1 is a somatic and cancer stem cell determinant.

Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell fu...

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Main Authors: Jessica Maddox, Arvind Shakya, Samuel South, Dawne Shelton, Jared N Andersen, Stephanie Chidester, Jinsuk Kang, Keith M Gligorich, David A Jones, Gerald J Spangrude, Bryan E Welm, Dean Tantin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003048&type=printable
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author Jessica Maddox
Arvind Shakya
Samuel South
Dawne Shelton
Jared N Andersen
Stephanie Chidester
Jinsuk Kang
Keith M Gligorich
David A Jones
Gerald J Spangrude
Bryan E Welm
Dean Tantin
author_facet Jessica Maddox
Arvind Shakya
Samuel South
Dawne Shelton
Jared N Andersen
Stephanie Chidester
Jinsuk Kang
Keith M Gligorich
David A Jones
Gerald J Spangrude
Bryan E Welm
Dean Tantin
author_sort Jessica Maddox
collection DOAJ
description Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI) cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI) cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.
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spelling doaj.art-0919bdc7bcae48b0ba2c398df15a22d42025-02-21T05:34:20ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01811e100304810.1371/journal.pgen.1003048Transcription factor Oct1 is a somatic and cancer stem cell determinant.Jessica MaddoxArvind ShakyaSamuel SouthDawne SheltonJared N AndersenStephanie ChidesterJinsuk KangKeith M GligorichDavid A JonesGerald J SpangrudeBryan E WelmDean TantinDefining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI) cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI) cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003048&type=printable
spellingShingle Jessica Maddox
Arvind Shakya
Samuel South
Dawne Shelton
Jared N Andersen
Stephanie Chidester
Jinsuk Kang
Keith M Gligorich
David A Jones
Gerald J Spangrude
Bryan E Welm
Dean Tantin
Transcription factor Oct1 is a somatic and cancer stem cell determinant.
PLoS Genetics
title Transcription factor Oct1 is a somatic and cancer stem cell determinant.
title_full Transcription factor Oct1 is a somatic and cancer stem cell determinant.
title_fullStr Transcription factor Oct1 is a somatic and cancer stem cell determinant.
title_full_unstemmed Transcription factor Oct1 is a somatic and cancer stem cell determinant.
title_short Transcription factor Oct1 is a somatic and cancer stem cell determinant.
title_sort transcription factor oct1 is a somatic and cancer stem cell determinant
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1003048&type=printable
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