C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells

Suzanne E.M. van der Horst; Janine Cravo; Alison Woollard; Juliane Teapal; Sander van den Heuvel

doi:10.1242/dev.180034

C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells

Suzanne E.M. van der Horst
, Janine Cravo
, Alison Woollard
, Juliane Teapal
, Sander van den Heuvel^*

^*Corresponding author for this work

Oxford University

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1^TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1^Runx and cofactor BRO-1^CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/ CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.

Original language	English
Article number	dev180034
Pages (from-to)	1-14
Number of pages	14
Journal	Development (Cambridge)
Volume	146
Issue number	22
DOIs	https://doi.org/10.1242/dev.180034
Publication status	Published - 15 Nov 2019

Bibliographical note

Funding Information:
This work was supported by grants to S.v.d.H. from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Chemical Sciences ECHO project 711.010.110 and Fundamenteel Onderzoek der Materie NOISE program); from the Innovative Training Network (ITN) “PolarNet”, funded by H2020 Marie Sklodowska-Curie Actions 675407EU to S.v.d.H.; and by the Biotechnology and Biological Sciences Research Council grant BB/G018448/1 awarded to A.W. Deposited in PMC for immediate release.

Funding Information:
The authors thank members of the van den Heuvel, Boxem and Woollard labs for help and discussion. We thank Eugene Katrukah (A. Akhmanova lab) for help and expertise with analyzing fluorescence intensities. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440).

Publisher Copyright:
© 2019. Published by The Company of Biologists Ltd

Funding

This work was supported by grants to S.v.d.H. from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Chemical Sciences ECHO project 711.010.110 and Fundamenteel Onderzoek der Materie NOISE program); from the Innovative Training Network (ITN) “PolarNet”, funded by H2020 Marie Sklodowska-Curie Actions 675407EU to S.v.d.H.; and by the Biotechnology and Biological Sciences Research Council grant BB/G018448/1 awarded to A.W. Deposited in PMC for immediate release. The authors thank members of the van den Heuvel, Boxem and Woollard labs for help and discussion. We thank Eugene Katrukah (A. Akhmanova lab) for help and expertise with analyzing fluorescence intensities. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440).

Keywords

Asymmetric cell division
C. elegans
Runx
Stem cell division mode
Transcriptional regulation
Wnt signaling

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title = "C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells",

abstract = "A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1Runx and cofactor BRO-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/ CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.",

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author = "\{van der Horst\}, \{Suzanne E.M.\} and Janine Cravo and Alison Woollard and Juliane Teapal and \{van den Heuvel\}, Sander",

note = "Funding Information: This work was supported by grants to S.v.d.H. from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Chemical Sciences ECHO project 711.010.110 and Fundamenteel Onderzoek der Materie NOISE program); from the Innovative Training Network (ITN) “PolarNet”, funded by H2020 Marie Sklodowska-Curie Actions 675407EU to S.v.d.H.; and by the Biotechnology and Biological Sciences Research Council grant BB/G018448/1 awarded to A.W. Deposited in PMC for immediate release. Funding Information: The authors thank members of the van den Heuvel, Boxem and Woollard labs for help and discussion. We thank Eugene Katrukah (A. Akhmanova lab) for help and expertise with analyzing fluorescence intensities. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440). Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd",

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AU - Cravo, Janine

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AU - Teapal, Juliane

AU - van den Heuvel, Sander

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N2 - A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1Runx and cofactor BRO-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/ CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.

AB - A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1Runx and cofactor BRO-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/ CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.

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KW - Stem cell division mode

KW - Transcriptional regulation

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JO - Development (Cambridge)

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M1 - dev180034

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C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells

Abstract

Bibliographical note

Funding

Keywords

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