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  1. Article ; Online: Hallmarks of stemness in mammalian tissues.

    Beumer, Joep / Clevers, Hans

    Cell stem cell

    2024  Volume 31, Issue 1, Page(s) 7–24

    Abstract: All adult tissues experience wear and tear. Most tissues can compensate for cell loss through the activity of resident stem cells. Although the cellular maintenance strategies vary greatly between different adult (read: postnatal) tissues, the function ... ...

    Abstract All adult tissues experience wear and tear. Most tissues can compensate for cell loss through the activity of resident stem cells. Although the cellular maintenance strategies vary greatly between different adult (read: postnatal) tissues, the function of stem cells is best defined by their capacity to replace lost tissue through division. We discuss a set of six complementary hallmarks that are key enabling features of this basic function. These include longevity and self-renewal, multipotency, transplantability, plasticity, dependence on niche signals, and maintenance of genome integrity. We discuss these hallmarks in the context of some of the best-understood adult stem cell niches.
    MeSH term(s) Animals ; Mammals ; Stem Cell Niche ; Stem Cells
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2023.12.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cell fate specification and differentiation in the adult mammalian intestine.

    Beumer, Joep / Clevers, Hans

    Nature reviews. Molecular cell biology

    2020  Volume 22, Issue 1, Page(s) 39–53

    Abstract: Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal ... ...

    Abstract Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal contents. Recent discoveries have revealed that the lineage plasticity of committed cells - combined with redundant sources of niche signals - enables the epithelium to efficiently repair tissue damage. New approaches such as single-cell transcriptomics and the use of organoid models have led to the identification of the signals that guide fate specification of stem cell progeny into the six intestinal cell lineages. These cell types display context-dependent functionality and can adapt to different requirements over their lifetime, as dictated by their microenvironment. These new insights into stem cell regulation and fate specification could aid the development of therapies that exploit the regenerative capacity and functionality of the gut.
    MeSH term(s) Animals ; Cell Differentiation ; Cell Lineage ; Humans ; Intestinal Mucosa/cytology ; Regeneration ; Signal Transduction ; Stem Cells/cytology
    Language English
    Publishing date 2020-09-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-020-0278-0
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  3. Article ; Online: ROCKin' Intestinal Cell Fate: A Potential Avenue to Improve Glucose Sensitivity.

    Beumer, Joep / Clevers, Hans

    Gastroenterology

    2018  Volume 155, Issue 4, Page(s) 974–976

    MeSH term(s) Cell Differentiation ; Glucose ; Intestines
    Chemical Substances Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2018-09-08
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2018.09.005
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  4. Article ; Online: Enteroendocrine Dynamics - New Tools Reveal Hormonal Plasticity in the Gut.

    Beumer, Joep / Gehart, Helmuth / Clevers, Hans

    Endocrine reviews

    2020  Volume 41, Issue 5

    Abstract: The recent intersection of enteroendocrine cell biology with single-cell technologies and novel in vitro model systems has generated a tremendous amount of new data. Here we highlight these recent developments and explore how these findings contribute to ...

    Abstract The recent intersection of enteroendocrine cell biology with single-cell technologies and novel in vitro model systems has generated a tremendous amount of new data. Here we highlight these recent developments and explore how these findings contribute to the understanding of endocrine lineages in the gut. In particular, the concept of hormonal plasticity, the ability of endocrine cells to produce different hormones over the course of their lifetime, challenges the classic notion of cell types. Enteroendocrine cells travel in the course of their life through different signaling environments that directly influence their hormonal repertoire. In this context, we examine how enteroendocrine cell fate is determined and modulated by signaling molecules such as bone morphogenetic proteins (BMPs) or location along the gastrointestinal tract. We analyze advantages and disadvantages of novel in vitro tools, adult stem cell or iPS-derived intestinal organoids, that have been crucial for recent findings on enteroendocrine development and plasticity. Finally, we illuminate the future perspectives of the field and discuss how understanding enteroendocrine plasticity can lead to new therapeutic approaches.
    MeSH term(s) Adult Stem Cells ; Animals ; Cells, Cultured ; Enteroendocrine Cells/cytology ; Enteroendocrine Cells/metabolism ; Enteroendocrine Cells/physiology ; Gastrointestinal Tract/cytology ; Gastrointestinal Tract/metabolism ; Gastrointestinal Tract/physiology ; Hormones/metabolism ; Humans ; Induced Pluripotent Stem Cells ; Models, Biological ; Organoids
    Chemical Substances Hormones
    Language English
    Publishing date 2020-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603096-8
    ISSN 1945-7189 ; 0163-769X
    ISSN (online) 1945-7189
    ISSN 0163-769X
    DOI 10.1210/endrev/bnaa018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: How the Gut Feels, Smells, and Talks.

    Beumer, Joep / Clevers, Hans

    Cell

    2017  Volume 170, Issue 1, Page(s) 10–11

    Abstract: Gut-brain signaling plays a central role in a range of homeostatic processes, yet details of this cross-talk remain enigmatic. In this issue of Cell, Bellono and colleagues identify a variety of luminal stimuli acting on serotonin-secreting ... ...

    Abstract Gut-brain signaling plays a central role in a range of homeostatic processes, yet details of this cross-talk remain enigmatic. In this issue of Cell, Bellono and colleagues identify a variety of luminal stimuli acting on serotonin-secreting enteroendocrine cells and, for the first time, demonstrate a functional synaptic interaction with neurons.
    MeSH term(s) Enteroendocrine Cells ; Serotonin ; Signal Transduction ; Smell
    Chemical Substances Serotonin (333DO1RDJY)
    Language English
    Publishing date 2017--29
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.06.023
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  6. Article ; Online: The Organoid Platform: Promises and Challenges as Tools in the Fight against COVID-19.

    Geurts, Maarten H / van der Vaart, Jelte / Beumer, Joep / Clevers, Hans

    Stem cell reports

    2021  Volume 16, Issue 3, Page(s) 412–418

    Abstract: Many pathogenic viruses that affect man display species specificity, limiting the use of animal models. Studying viral biology and identifying potential treatments therefore benefits from the development of in vitro cell systems that closely mimic human ... ...

    Abstract Many pathogenic viruses that affect man display species specificity, limiting the use of animal models. Studying viral biology and identifying potential treatments therefore benefits from the development of in vitro cell systems that closely mimic human physiology. In the current COVID-19 pandemic, rapid scientific insights are of the utmost importance to limit its impact on public health and society. Organoids are emerging as versatile tools to progress the understanding of SARS-CoV-2 biology and to aid in the quest for novel treatments.
    MeSH term(s) Animals ; COVID-19/virology ; Humans ; Organoids/virology ; Pandemics/prevention & control ; SARS-CoV-2/pathogenicity
    Language English
    Publishing date 2021-03-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2720528-9
    ISSN 2213-6711 ; 2213-6711
    ISSN (online) 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2020.11.009
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  7. Article ; Online: Regulation and plasticity of intestinal stem cells during homeostasis and regeneration.

    Beumer, Joep / Clevers, Hans

    Development (Cambridge, England)

    2016  Volume 143, Issue 20, Page(s) 3639–3649

    Abstract: The intestinal epithelium is the fastest renewing tissue in mammals and has a large flexibility to adapt to different types of damage. ... ...

    Abstract The intestinal epithelium is the fastest renewing tissue in mammals and has a large flexibility to adapt to different types of damage. Lgr5
    MeSH term(s) Animals ; Homeostasis/genetics ; Homeostasis/physiology ; Humans ; Intestines/cytology ; Intestines/metabolism ; Regeneration/genetics ; Regeneration/physiology ; Signal Transduction/genetics ; Signal Transduction/physiology ; Stem Cells/cytology ; Stem Cells/metabolism
    Language English
    Publishing date 2016--15
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.133132
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  8. Article: How the Gut Feels, Smells, and Talks

    Beumer, Joep / Hans Clevers

    Cell. 2017 June 29, v. 170

    2017  

    Abstract: Gut-brain signaling plays a central role in a range of homeostatic processes, yet details of this cross-talk remain enigmatic. In this issue of Cell, Bellono and colleagues identify a variety of luminal stimuli acting on serotonin-secreting ... ...

    Abstract Gut-brain signaling plays a central role in a range of homeostatic processes, yet details of this cross-talk remain enigmatic. In this issue of Cell, Bellono and colleagues identify a variety of luminal stimuli acting on serotonin-secreting enteroendocrine cells and, for the first time, demonstrate a functional synaptic interaction with neurons.
    Keywords brain ; cell communication ; digestive system ; endocrine system ; neurons ; serotonin ; synapse
    Language English
    Dates of publication 2017-0629
    Size p. 10-11.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.06.023
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  9. Article ; Online: Tubuloid differentiation to model the human distal nephron and collecting duct in health and disease.

    Yousef Yengej, Fjodor A / Pou Casellas, Carla / Ammerlaan, Carola M E / Olde Hanhof, Charlotte J A / Dilmen, Emre / Beumer, Joep / Begthel, Harry / Meeder, Elise M G / Hoenderop, Joost G / Rookmaaker, Maarten B / Verhaar, Marianne C / Clevers, Hans

    Cell reports

    2023  Volume 43, Issue 1, Page(s) 113614

    Abstract: Organoid technology is rapidly gaining ground for studies on organ (patho)physiology. Tubuloids are long-term expanding organoids grown from adult kidney tissue or urine. The progenitor state of expanding tubuloids comes at the expense of differentiation. ...

    Abstract Organoid technology is rapidly gaining ground for studies on organ (patho)physiology. Tubuloids are long-term expanding organoids grown from adult kidney tissue or urine. The progenitor state of expanding tubuloids comes at the expense of differentiation. Here, we differentiate tubuloids to model the distal nephron and collecting ducts, essential functional parts of the kidney. Differentiation suppresses progenitor traits and upregulates genes required for function. A single-cell atlas reveals that differentiation predominantly generates thick ascending limb and principal cells. Differentiated human tubuloids express luminal NKCC2 and ENaC capable of diuretic-inhibitable electrolyte uptake and enable disease modeling as demonstrated by a lithium-induced tubulopathy model. Lithium causes hallmark AQP2 loss, induces proliferation, and upregulates inflammatory mediators, as seen in vivo. Lithium also suppresses electrolyte transport in multiple segments. In conclusion, this tubuloid model enables modeling of the human distal nephron and collecting duct in health and disease and provides opportunities to develop improved therapies.
    MeSH term(s) Adult ; Humans ; Lithium/pharmacology ; Aquaporin 2 ; Nephrons ; Kidney ; Electrolytes ; Organoids
    Chemical Substances Lithium (9FN79X2M3F) ; Aquaporin 2 ; Electrolytes
    Language English
    Publishing date 2023-12-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models.

    Mykytyn, Anna Z / Breugem, Tim I / Geurts, Maarten H / Beumer, Joep / Schipper, Debby / van Acker, Romy / van den Doel, Petra B / van Royen, Martin E / Zhang, Jingshu / Clevers, Hans / Haagmans, Bart L / Lamers, Mart M

    Journal of virology

    2023  Volume 97, Issue 8, Page(s) e0085123

    Abstract: SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters cells ...

    Abstract SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters cells via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for Omicron in a monkey kidney cell line, experiments with protease inhibitors showed that Omicron (BA.1 and XBB1.5) did not use cathepsins for entry into human airway organoids and instead utilized TTSPs. Likewise, CRISPR-edited intestinal organoids showed that entry of Omicron BA.1 relied on the expression of the serine protease TMPRSS2 but not cathepsin L or B. Together, these data force us to rethink the concept that Omicron has adapted to cathepsin-mediated entry and indicate that TTSP inhibitors should not be dismissed as prophylactic or therapeutic antiviral strategy against SARS-CoV-2. IMPORTANCE Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Whereas earlier studies using cell lines suggested that the Omicron variant of SARS-CoV-2 has changed its protease usage, from cell surface type II transmembrane serine proteases (TTSPs) to endosomal cathepsins, we report that this is not the case in human airway and intestinal organoid models, suggesting that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlighting the importance of relevant human
    MeSH term(s) Humans ; Antiviral Agents ; COVID-19/virology ; SARS-CoV-2/physiology ; Serine Proteases/metabolism ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization
    Chemical Substances Antiviral Agents ; Serine Proteases (EC 3.4.-) ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; TMPRSS2 protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2023-08-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00851-23
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