An ancient defense system eliminates unfit cells from developing tissues during cell competition

Meyer, Stefan; Amoyel, Marc; Bergantiños, Cora; Cova, Claire de la; Schertel, Claus; Basler, Konrad; Johnston, Laura

doi:10.1126/science.1258236

Cited by 206 publications

(290 citation statements)

References 47 publications

(97 reference statements)

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“…Increased p53 activity was achieved by deletion of one Mdm2 allele, which conferred significant disadvantage to HSPCs cotransplanted with WT HSPCs [149]. Cellular competition is often based on induction of apoptosis in 'loser' cells [141,150,151]. Hematopoietic competition mediated by p53, however, seemed not to require killing of outcompeted cells as overexpression of Bcl-2 in the hematopoietic compartment did not influence bone marrow chimerism, and apoptosis-related genes such as Puma and Bax were not differentially regulated in the competing cell populations.…”

Section: The Role Of P53 Beyond Dna Damage Responsementioning

confidence: 99%

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

et al. 2016

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Members of the Bcl‐2 protein family regulate cell fate decisions following a variety of developmental cues or stress signals, with the outcomes of cell death or survival, thus shaping multiple mammalian tissues. This review describes in detail how anti‐ and proapoptotic Bcl‐2 proteins contribute to the development and functioning of the fetal and adult hematopoietic systems and how they influence the generation and maintenance of different hematopoietic lineages. An overview on how stress signals such as genotoxic stress or inflammation can compromise blood cell production, partially by engaging the intrinsic apoptosis pathway, is presented. Finally, the review describes how Bcl‐2 protein deregulation—either leading to increased apoptosis resistance or excessive cell death—contributes to many hematological disorders, with specific focus on rare disorders of hematopoiesis and how this knowledge may be used therapeutically.

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Section: The Role Of P53 Beyond Dna Damage Responsementioning

confidence: 99%

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

et al. 2016

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“…After a genomic screen designed to discover genes required for cell competition, Rhiner et al, identified flower (fwe), a gene encoding a trans-membrane protein that also appears to be implicated in synaptic vesicle exo-and endocytosis (Yao et al, 2009). fwe generates three RNA forms, a ubiquitous one, fwe ubi , and two others, fwe Lose A and fwe Lose B , which are up regulated in loser cells during cell competition (Rhiner et al, 2010) (Meyer et al, 2014). Normally Toll and Imd activate genes encoding antimicrobial peptides, aimed to eliminate foreign pathogens like bacteria or fungi; but to eliminate loser cells this novel pathway activates the pro-apoptotic genes reaper and hid.…”

Section: Mechanisms Of Cell Competitionmentioning

confidence: 99%

Cell competition, apoptosis and tumour development

Morata

Ballesteros-Arias²

2015

Int. J. Dev. Biol.

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The phenomenon of cell competition is an interactive process originally discovered in the imaginal discs of Drosophila; it is a developmental mechanism that identifies and eliminates cells that are weaker than their neighbours or have features that make them different or not well adapted to their surroundings. It appears to be an important homeostatic mechanism to contribute to the general fitness of developing tissues. Here we discuss some of the basic features of cell competition and then focus on results indicating that cell competition is responsible for the removal of malignant or aberrant cells that may appear during development, although in certain circumstances it can revert its role to promote tumour growth. We also consider several recent studies that indicate that cell competition also occurs in vertebrates where it performs similar functions.

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“…61 It has only recently been shown that this competition relies on TOLL signaling inducing NFκB-dependent apoptosis in 'loser' cells and their subsequent engulfment by 'winner' cells. 62,63 Along this line, a natural cell competition has been described for thymic progenitor cells in the mouse. Young cells recently immigrated from bone marrow displace 'older' progenitors already residing in the thymus.…”

Section: The Apoptosis Paradox In Tumor Developmentmentioning

confidence: 99%

How cell death shapes cancer

Erlacher

2015

Klin Padiatr

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Apoptosis has been established as a mechanism of anti-cancer defense. Members of the BCL-2 family are critical mediators of apoptotic cell death in health and disease, often found to be deregulated in cancer and believed to lead to the survival of malignant clones. However, over the years, a number of studies pointed out that a model in which cell death resistance unambiguously acts as a barrier against malignant disease might be too simple. This is based on paradoxical observations made in tumor patients as well as mouse models indicating that apoptosis can indeed drive tumor formation, at least under certain circumstances. One possible explanation for this phenomenon is that apoptosis can promote proliferation critically needed to compensate for cell loss, for example, upon therapy, and to restore tissue homeostasis. However, this, at the same time, can promote tumor development by allowing expansion of selected clones. Usually, tissue resident stem/progenitor cells are a major source for repopulation, some of them potentially carrying (age-, injury-or therapy-induced) genetic aberrations deleterious for the host. Thereby, apoptosis might drive genomic instability by facilitating the emergence of pathologic clones during phases of proliferation and subsequent replication stress-associated DNA damage. Tumorigenesis initiated by repeated cell attrition and repopulation, as confirmed in different genetic models, has parallels in human cancers, exemplified in therapy-induced secondary malignancies and myelodysplastic syndromes in patients with congenital bone marrow failure syndromes. Here, we aim to review evidence in support of the oncogenic role of stress-induced apoptosis.

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An ancient defense system eliminates unfit cells from developing tissues during cell competition

Cited by 206 publications

References 47 publications

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

Cell competition, apoptosis and tumour development

How cell death shapes cancer

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