Cell plasticity in <i>Caenorhabditis elegans</i>: From induced to natural cell reprogramming

Hajdůšková, Martina; Ahier, Arnaud; Daniele, Thomas; Jarriault, Sophie

doi:10.1002/dvg.20806

Cited by 17 publications

(11 citation statements)

References 82 publications

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“…A number of studies have shown how strikingly easily a differentiated cell can be experimentally reprogrammed not only into an embryonic stem cell-like state (1) but also into another, different, differentiated identity (2). Remarkably, this process, called direct cell-type conversion or transdifferentiation, also occurs naturally (2).…”

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confidence: 99%

Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

Kagias

Ahier

Fischer

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Differentiated cells can be forced to change identity, either to directly adopt another differentiated identity or to revert to a pluripotent state. Direct reprogramming events can also occur naturally. We recently characterized such an event in Caenorhabditis elegans, in which a rectal cell switches to a neuronal cell. Here we have used this single-cell paradigm to investigate the molecular requirements of direct cell-type conversion, with a focus on the early steps. Our genetic analyses revealed the requirement of sem-4/Sall, egl-27/ Mta, and ceh-6/Oct, members of the NODE complex recently identified in embryonic stem (ES) cells, and of the OCT4 partner sox-2, for the initiation of this natural direct reprogramming event. These four factors have been shown to individually impact on ES cell pluripotency; however, whether they act together to control cellular potential during development remained an open question. We further found that, in addition to acting at the same time, these factors physically associate, suggesting that they could act together as a NODE-like complex during this in vivo process. Finally, we have elucidated the functional domains in EGL-27/MTA that mediate its reprogramming activity in this system and have found that modulation of the posterior HOX protein EGL-5 is a downstream event to allow the initiation of Y identity change. Our data reveal unique in vivo functions in a natural direct reprogramming event for these genes that impact on ES cells pluripotency and suggest that conserved nuclear events could be shared between different cell plasticity phenomena across phyla.transdifferentiation | regenerative medicine | metaplasia | SANT H ow differentiated cells can switch their identity is a fascinating question that has attracted much attention in the last decade. A number of studies have shown how strikingly easily a differentiated cell can be experimentally reprogrammed not only into an embryonic stem cell-like state (1) but also into another, different, differentiated identity (2). Remarkably, this process, called direct cell-type conversion or transdifferentiation, also occurs naturally (2).The molecular mechanisms underlying these events are still unclear and it remains to be determined whether key elements are shared between natural and induced reprogramming events. Factors used to reprogram differentiated cells to a stem cell-like state are important for embryonic stem (ES) cell self-renewal (1). Several studies have shed light on the molecular networks that maintain ES cell pluripotency (3). Key factors have been identified, such as Nanog (3) or SOX2 and OCT4 that are required for ES cell pluripotency and that, together with additional factors, can force fibroblasts into embryonic-like stem cells (1, 3). Besides these pluripotency factors, transcriptional repression complexes have been found necessary for ES cell self-renewal, but whether and how these complexes act together to control cellular potential during development remain to be determined. Among them, the NODE (Nanog and O...

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confidence: 99%

Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

Kagias

Ahier

Fischer

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…For this proof-of-principle experiment, we decided to rescue a specific biological process: the Y-to-PDA transdifferentiation event, a model developed and characterized in the laboratory, where a single rectal epithelial cell called Y becomes a motorneuron called PDA during the L2 stage (Richard et al 2011;Hajduskova et al 2012;Zuryn et al 2012) We have shown that SEM-4 (a homolog of SALL) is crucial for the initiation of this reprogramming event as a member of a NODE-like complex (Jarriault et al 2008;. The sem-4(n1971) mutant, in which Y-to-PDA is 100% defective, can be rescued by expressing col-34p::sem-4a::HA::SL2::mCherry .…”

Section: A Peptides Can Simultaneously Deliver Five Distinct Functiomentioning

confidence: 99%

Simultaneous Expression of Multiple Proteins Under a Single Promoter in Caenorhabditis elegans via a Versatile 2A-Based Toolkit

2014

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Caenorhabditis elegans is a powerful in vivo model in which transgenesis is highly developed. However, while the analysis of biological phenomena often require the expression of more than one protein of interest, no reliable tool exists to ensure efficient concomitant and equivalent expression of more than two polypeptides from a single promoter. We report the use of viral 2A peptides, which trigger a "ribosomal-skip" or "STOP&GO" mechanism during translation, to express multiple proteins from a single vector in C. elegans. Although none of the viruses known to infect C. elegans contain 2A-like sequences, our results show that 2A peptides allow the production of separate functional proteins in all cell types and at all developmental stages tested in the worm. In addition, we constructed a toolkit including a 2A-based polycistronic plasmid and reagents to generate 2A-tagged fosmids. 2A peptides constitute an important tool to ensure the delivery of multiple polypeptides in specific cells, enabling several novel applications such as the reconstitution of multi-subunit complexes.

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“… 78,79 Furthermore, various manipulations have been used to stimulate reprogramming of cells into a desired phenotype. 80 Notably, a few years ago it was demonstrated that depletion of GLD-1 and MEX-3, or GLD-1 alone, causes germ cells to ectopically transdifferentiate into various somatic cell types, forming human germ cell tumor-like teratomas. 67,81 However, epigenetic factors may confer resistance to efficient reprogramming to specific cell types.…”

Section: Alterations In Cell Death Pathways and Their Implications Inmentioning

confidence: 99%

Caenorhabditis elegansas a model for cancer research

Kyriakakis

Markaki

Tavernarakis

2014

Molecular & Cellular Oncology

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The term cancer describes a group of multifaceted diseases characterized by an intricate pathophysiology. Despite significant advances in the fight against cancer, it remains a key public health concern and burden on societies worldwide. Elucidation of key molecular and cellular mechanisms of oncogenic diseases will facilitate the development of better intervention strategies to counter or prevent tumor development. In vivo and in vitro models have long been used to delineate distinct biological processes involved in cancer such as apoptosis, proliferation, angiogenesis, invasion, metastasis, genome instability, and metabolism. In this review, we introduce Caenorhabditis elegans as an emerging animal model for systematic dissection of the molecular basis of tumorigenesis, focusing on the well-established processes of apoptosis and autophagy. Additionally, we propose that C. elegans can be used to advance our understanding of cancer progression, such as deregulation of energy metabolism, stem cell reprogramming, and host–microflora interactions.

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Cell plasticity in Caenorhabditis elegans: From induced to natural cell reprogramming

Cited by 17 publications

References 82 publications

Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

Simultaneous Expression of Multiple Proteins Under a Single Promoter in Caenorhabditis elegans via a Versatile 2A-Based Toolkit

Caenorhabditis elegansas a model for cancer research

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