The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation
Summary: Drosophila POU/Oct transcription factors are required for many developmental processes, but their putative regulation of adult stem cell activity has not been investigated. Here, we show that Nubbin (Nub)/Pdm1, homologous to mammalian OCT1/POU2F1 and related to OCT4/POU5F1, is expressed in...
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doaj-af8808fd6c9047f3a814a097e20215642020-11-25T01:09:32ZengElsevierStem Cell Reports2213-67112018-05-0110515651578The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific RegulationXiongzhuo Tang0Yunpo Zhao1Nicolas Buchon2Ylva Engström3Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 10691, SwedenDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 10691, SwedenDepartment of Entomology, Cornell University, Ithaca, NY 14853, USADepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm 10691, Sweden; Corresponding authorSummary: Drosophila POU/Oct transcription factors are required for many developmental processes, but their putative regulation of adult stem cell activity has not been investigated. Here, we show that Nubbin (Nub)/Pdm1, homologous to mammalian OCT1/POU2F1 and related to OCT4/POU5F1, is expressed in gut epithelium progenitor cells. We demonstrate that the nub-encoded protein isoforms, Nub-PB and Nub-PD, play opposite roles in the regulation of intestinal stem cell (ISC) maintenance and differentiation. Depletion of Nub-PB in progenitor cells increased ISC proliferation by derepression of escargot expression. Conversely, loss of Nub-PD reduced ISC proliferation, suggesting that this isoform is necessary for ISC maintenance, analogous to mammalian OCT4/POU5F1 functions. Furthermore, Nub-PB is required in enteroblasts to promote differentiation, and it acts as a tumor suppressor of Notch RNAi-driven hyperplasia. We suggest that a dynamic and well-tuned expression of Nub isoforms in progenitor cells is required for maintaining gut epithelium homeostasis. : Engström and colleagues show that Drosophila Nubbin, a homolog of mammalian OCT1 and OCT4, controls stem cell proliferation and differentiation in the fly midgut. Two isoforms, Nub-PB and Nub-PD, regulate progenitor cell fate antagonistically, as loss of Nub-PB provokes hyperplasia, while loss of Nub-PD blocks stem cell proliferation. In addition, Nub-PB acts as a differentiation factor and strong tumor suppressor. Keywords: Pdm1, POU, homeodomain, Drosophila, stem cell, epithelium regeneration, Escargot, Notch, mitosis, midbodyhttp://www.sciencedirect.com/science/article/pii/S2213671118301413 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiongzhuo Tang Yunpo Zhao Nicolas Buchon Ylva Engström |
spellingShingle |
Xiongzhuo Tang Yunpo Zhao Nicolas Buchon Ylva Engström The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation Stem Cell Reports |
author_facet |
Xiongzhuo Tang Yunpo Zhao Nicolas Buchon Ylva Engström |
author_sort |
Xiongzhuo Tang |
title |
The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation |
title_short |
The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation |
title_full |
The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation |
title_fullStr |
The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation |
title_full_unstemmed |
The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation |
title_sort |
pou/oct transcription factor nubbin controls the balance of intestinal stem cell maintenance and differentiation by isoform-specific regulation |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2018-05-01 |
description |
Summary: Drosophila POU/Oct transcription factors are required for many developmental processes, but their putative regulation of adult stem cell activity has not been investigated. Here, we show that Nubbin (Nub)/Pdm1, homologous to mammalian OCT1/POU2F1 and related to OCT4/POU5F1, is expressed in gut epithelium progenitor cells. We demonstrate that the nub-encoded protein isoforms, Nub-PB and Nub-PD, play opposite roles in the regulation of intestinal stem cell (ISC) maintenance and differentiation. Depletion of Nub-PB in progenitor cells increased ISC proliferation by derepression of escargot expression. Conversely, loss of Nub-PD reduced ISC proliferation, suggesting that this isoform is necessary for ISC maintenance, analogous to mammalian OCT4/POU5F1 functions. Furthermore, Nub-PB is required in enteroblasts to promote differentiation, and it acts as a tumor suppressor of Notch RNAi-driven hyperplasia. We suggest that a dynamic and well-tuned expression of Nub isoforms in progenitor cells is required for maintaining gut epithelium homeostasis. : Engström and colleagues show that Drosophila Nubbin, a homolog of mammalian OCT1 and OCT4, controls stem cell proliferation and differentiation in the fly midgut. Two isoforms, Nub-PB and Nub-PD, regulate progenitor cell fate antagonistically, as loss of Nub-PB provokes hyperplasia, while loss of Nub-PD blocks stem cell proliferation. In addition, Nub-PB acts as a differentiation factor and strong tumor suppressor. Keywords: Pdm1, POU, homeodomain, Drosophila, stem cell, epithelium regeneration, Escargot, Notch, mitosis, midbody |
url |
http://www.sciencedirect.com/science/article/pii/S2213671118301413 |
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