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...
Main Authors: | , , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
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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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id | doaj.art-0919bdc7bcae48b0ba2c398df15a22d4 |
institution | Directory Open Access Journal |
issn | 1553-7390 1553-7404 |
language | English |
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publishDate | 2012-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Genetics |
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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