title: Transcription factor Oct1 is a somatic and cancer stem cell determinant.
abstract: 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.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Maddox
authors.forename: Arvind
authors.initials: A
authors.lastname: Shakya
authors.forename: Samuel
authors.initials: S
authors.lastname: South
authors.forename: Dawne
authors.initials: D
authors.lastname: Shelton
authors.forename: Jared N
authors.initials: JN
authors.lastname: Andersen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chidester
authors.forename: Jinsuk
authors.initials: J
authors.lastname: Kang
authors.forename: Keith M
authors.initials: KM
authors.lastname: Gligorich
authors.forename: David A
authors.initials: DA
authors.lastname: Jones
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Spangrude
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Welm
authors.forename: Dean
authors.initials: D
authors.lastname: Tantin
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger; D000444:Aldehyde Dehydrogenase