4.8 Article

Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

Journal

ELIFE
Volume 8, Issue -, Pages -

Publisher

ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.48561

Keywords

-

Categories

Funding

  1. Francis Crick Institute [FC0010089]
  2. Medical Research Council [U117570528]
  3. Wellcome [106187/Z/14/Z]
  4. H2020 Marie Sklodowska-Curie Actions Project [799214]
  5. Ligue Contre le Cancer [PJA 20131200481, PJA 20151203259]
  6. H2020 Marie Sklodowska-Curie Actions [H2020-MSCA-IF-2014]
  7. Marie Curie Actions (MSCA) [799214] Funding Source: Marie Curie Actions (MSCA)
  8. MRC [MR/M023907/1] Funding Source: UKRI
  9. Wellcome Trust [106187/Z/14/Z] Funding Source: Wellcome Trust

Ask authors/readers for more resources

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Cell & Tissue Engineering

Integrative and perturbation based analysis of the transcriptional dynamics of TGFβ/BMP system components in transition from embryonic stem cells to neural progenitors

Ruben Dries, Agata Stryjewska, Kathleen Coddens, Satoshi Okawa, Tineke Notelaers, Judith Birkhoff, Mike Dekker, Catherine M. Verfaillie, Antonio del Sol, Eskeatnaf Mulugeta, Andrea Conidi, Frank G. Grosveld, Danny Huylebroeck

STEM CELLS (2020)

Article Hematology

An evolutionarily ancient mechanism for regulation of hemoglobin expression in vertebrate red cells

Masato Miyata, Nynke Gillemans, Dorit Hockman, Jeroen A. A. Demmers, Jan -Fang Cheng, Jun Hou, Matti Salminen, Christopher A. Fisher, Stephen Taylor, Richard J. Gibbons, Jared J. Ganis, Leonard I. Zon, Frank Grosveld, Eskeatnaf Mulugeta, Tatjana Sauka-Spengler, Douglas R. Higgs, Sjaak Philipsen

BLOOD (2020)

Article Cell Biology

MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome

Ilaria Parenti, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina Casa, Riccardo Berutti, Rutger W. W. Brouwer, Valerie Dupe, Juliane Eckhold, Elisabeth Graf, Beatriz Puisac, Feliciano Ramos, Thomas Schwarzmayr, Macarena Moronta Gines, Thomas van Staveren, Wilfred F. J. van IJcken, Tim M. Strom, Juan Pie, Erwan Watrin, Frank J. Kaiser, Kerstin S. Wendt

CELL REPORTS (2020)

Article Cell Biology

The Bone-Forming Properties of Periosteum-Derived Cells Differ Between Harvest Sites

Lisanne C. Groeneveldt, Tim Herpelinck, Marina Marechal, Constantinus Politis, Wilfred F. J. van IJcken, Danny Huylebroeck, Liesbet Geris, Eskeatnaf Mulugeta, Frank P. Luyten

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

Article Cell & Tissue Engineering

Coordinated changes in cellular behavior ensure the lifelong maintenance of the hippocampal stem cell population

Lachlan Harris, Piero Rigo, Thomas Stiehl, Zachary B. Gaber, Sophie H. L. Austin, Maria del Mar Masdeu, Amelia Edwards, Noelia Urban, Anna Marciniak-Czochra, Francois Guillemot

Summary: The stabilization of neural stem cell numbers in young adults is a result of coordinated changes in stem cell behavior, with resting cells having a higher activation rate and greater contribution to neurogenesis. This change is associated with a progressive reduction in expression of the pro-activation protein ASCL1 due to increased post-translational degradation, providing insights into hippocampal NSC dynamics and neurogenesis rates in different mammalian species, including humans.

CELL STEM CELL (2021)

Review Developmental Biology

Stem cell quiescence: the challenging path to activation

Noelia Urban, Tom H. Cheung

Summary: Quiescence is a cellular state where a cell is out of the cell cycle but can still divide, and adult stem cells' ability to maintain quiescence is vital for tissue homeostasis and regeneration. Recent studies show that quiescence is an actively regulated process, and adult stem cells are sensitive to external stimuli. This has raised hopes of enhancing the reactivation potential of adult stem cells for improving tissue function during aging.

DEVELOPMENT (2021)

Article Cardiac & Cardiovascular Systems

Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis

Willeke de Haan, Wouter Dheedene, Katerina Apelt, Sofiane Decombas-Deschamps, Stefan Vinckier, Stefaan Verhulst, Andrea Conidi, Thomas Deffieux, Michael W. Staring, Petra Vandervoort, Ellen Caluwe, Marleen Lox, Inge Mannaerts, Tsuyoshi Takagi, Joris Jaekers, Geert Berx, Jody Haigh, Baki Topal, An Zwijsen, Yujiro Higashi, Leo A. van Grunsven, Wilfred F. J. van IJcken, Eskeatnaf Mulugeta, Mickael Tanter, Franck P. G. Lebrin, Danny Huylebroeck, Aernout Luttun

Summary: This study demonstrated the specific role of Zeb2 in liver endothelial cells, showing that Zeb2 deficiency leads to significant changes in gene expression related to angiogenesis and potential promotion of endothelial dedifferentiation. Furthermore, Zeb2 regulates LSEC-HSC communication and HSC activation to maintain vascular structure and inhibit liver fibrosis.

CARDIOVASCULAR RESEARCH (2022)

Article Developmental Biology

Wnt/β-catenin signalling is dispensable for adult neural stem cell homeostasis and activation

Sophie H. L. Austin, Rut Gabarro-Solanas, Piero Rigo, Oana Paun, Lachlan Harris, Francois Guillemot, Noelia Urban

Summary: Adult mouse hippocampal neural stem cells respond to Wnt/beta-catenin signaling, which can induce neuronal differentiation and activate or differentiate quiescent NSCs in a dose-dependent manner. However, the deletion of beta-catenin in NSCs does not affect their activation or maintenance of stem cell characteristics.

DEVELOPMENT (2021)

Article Neurosciences

Could a Different View of Quiescence Help Us Understand How Neurogenesis Is Regulated?

Noelia Urban

Summary: This article discusses the regulation of quiescence in adult neural stem cells (aNSCs) and proposes a dynamic transition model that acknowledges the complexity of aNSC states. The author emphasizes the need for a model that goes beyond simple activation transition in order to better understand the control of aNSC activity and neurogenesis.

FRONTIERS IN NEUROSCIENCE (2022)

Article Biology

DNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons

Lucile Marion-Poll, Jean-Pierre Roussarie, Lieng Taing, Cloelia Dard-Dascot, Nicolas Servant, Yan Jaszczyszyn, Emmanuelle Jordi, Eskeatnaf Mulugeta, Denis Herve, Deborah Bourc'his, Paul Greengard, Claude Thermes, Jean-Antoine Girault

Summary: Neuronal DNA modifications, including methylation outside CpG context and abundant 5-hydroxymethylation, show distinct patterns in striatal projection neurons expressing D1 or D2 dopamine receptors. DNA methylation differences mainly occur in large genomic clusters related to differentially expressed genes, while hydroxymethylation differences are scattered and affect transcription factor binding sites.

COMMUNICATIONS BIOLOGY (2022)

Article Biotechnology & Applied Microbiology

Retrospective analysis of enhancer activity and transcriptome history

Ruben Boers, Joachim Boers, Beatrice Tan, Marieke E. van Leeuwen, Evelyne Wassenaar, Erlantz Gonzalez Sanchez, Esther Sleddens, Yasha Tenhagen, Eskeatnaf Mulugeta, Joop Laven, Menno Creyghton, Willy Baarends, Wilfred F. J. van IJcken, Joost Gribnau

Summary: In this study, a bacterial methylation mark was used to label transcribed genes and active enhancers, allowing for tracking of cell state changes. This technique revealed rapid and coordinated activation of enhancers and nearby genes during enterocyte differentiation in the intestine. Furthermore, it provided insights into the chromatin landscape of intestinal stem cells and their differentiation process.

NATURE BIOTECHNOLOGY (2023)

Article Microbiology

STLV-1 Commonly Targets Neurons in the Brain of Asymptomatic Non-Human Primates

Brenda Rocamonde, Sandrine Alais, Rodolphe Pelissier, Valerie Moulin, Brigitte Rimbaud, Romain Lacoste, Noemie Aurine, Camille Baquerre, Bertrand Pain, Yuetsu Tanaka, Cyrille Mathieu, Helene Dutartre

Summary: The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The ability of HTLV-1 to infect cells in the central nervous system (CNS) and the resulting neuroimmune response have not been well-established. Using human induced pluripotent stem cells (hiPSC) and naturally infected nonhuman primates (NHP) as models, neuronal cells derived from hiPSC differentiation in neural polycultures were identified as the primary cell population infected by HTLV-1. Additionally, neuronal infection with STLV-1 was observed in spinal cord regions, as well as in brain cortical and cerebellar sections of postmortem NHP. Reactive microglial cells were also found in the infected areas, suggesting an immune antiviral response. These findings highlight the importance of developing more efficient models to understand HTLV-1 neuroinfection and propose an alternative mechanism for HAM/TSP.
Article Biology

Single-cell transcriptome sequencing allows genetic separation, characterization and identification of individuals in multi-person biological mixtures

Lucie Kulhankova, Diego Montiel Gonzalez, Eric Bindels, Daniel Kling, Manfred Kayser, Eskeatnaf Mulugeta

Summary: A method combining scRNA-sequencing and a bioinformatics pipeline was developed to separate individuals in multi-person biological mixtures and genetically identify them. This method showed success in separating individuals and determining their ancestry and sex in both de-novo generated and in-silico mixtures. The approach demonstrated the feasibility of single-cell approaches in deconvoluting biological mixtures and individually identifying the contributors, with potential application in crime scene investigation.

COMMUNICATIONS BIOLOGY (2023)

No Data Available