Induction of a Spindle-Assembly-Competent M Phase in Xenopus Egg Extracts

Bisht, Jitender S.; Tomschik, Miroslav; Gatlin, Jesse C.

doi:10.1016/j.cub.2019.02.061

Cited by 5 publications

(4 citation statements)

References 82 publications

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“…Among the highly downregulated genes were several proliferation factors, such as SOX2, NOTCH1, and OTX2 ( Figure 2—source data 3 ). Furthermore, the chromokinesin motor proteins KIF4a and KIF22, involved in cell proliferation through regulation of spindle microtubule dynamics during mitosis, were downregulated ( Almeida and Maiato, 2018 ; Bisht et al, 2019 ). Conversely, genes of several neuronal and axonal kinesins were upregulated, including KIF1a, KIF5c, and KIF21b ( Figure 2—source data 3 ; Hirokawa and Tanaka, 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Lindhout

Kooistra

Portegies

et al. 2020

eLife

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The differentiation of neuronal stem cells into polarized neurons is a well-coordinated process which has mostly been studied in classical non-human model systems, but to what extent these findings are recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured hiPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. The neuron transcriptome and proteome shows extensive remodeling, with differential expression profiles of ~1100 transcripts and ~2200 proteins during neuronal differentiation and polarization. We also identified a distinct axon developmental stage marked by the relocation of axon initial segment proteins and increased microtubule remodeling from the distal (stage 3a) to the proximal (stage 3b) axon. This developmental transition coincides with action potential maturation. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.

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Section: Resultsmentioning

confidence: 99%

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Lindhout

Kooistra

Portegies

et al. 2020

eLife

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“…Among the highly downregulated genes were several proliferation factors, such as SOX2, NOTCH1, and OTX2 (TABLE 3). Furthermore, the chromokinesin motor proteins KIF4a and KIF22, involved in cell proliferation by regulating spindle microtubule dynamics during mitosis, were downregulated (Almeida and Maiato 2018;Bisht, Tomschik, and Gatlin 2019). Conversely, genes of several neuronal and axonal kinesins are upregulated, including KIF1a, KIF5c, and KIF21b (TABLE 3) (Hirokawa and Tanaka 2015).…”

Section: Transcriptomic Profiling Of Developing Human Ipsc-derived Nementioning

confidence: 99%

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Lindhout

Kooistra

Portegies

et al. 2020

Preprint

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Early neuronal development is a well-coordinated process in which neuronal stem cells differentiate into polarized neurons. This process has been well studied in classical non-human model systems, but to what extent this is recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured human iPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. We found extensive remodeling of the neuron transcriptome and proteome, with altered mRNA expression of ~1,100 genes and different expression profiles of ~1,500 proteins during neuronal differentiation and polarization. We also identified a distinct stage in axon development marked by an increase in microtubule remodeling and apparent relocation of the axon initial segment from the distal to proximal axon. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.(FOM, #16NEPH05, CJW). AUTHOR CONTRIBUTIONSFWL, RK and SP designed the research, conducted experiments, and wrote the article together with LJH. RS conducted and analyzed the mass spectrometry experiments supervised by MA, LJH performed and interpreted the electrophysiology data supervised by CJW, RK and BLS provided and interpreted the RNA sequencing analysis. HDM edited the article. CCH designed the experimental plan, supervised the research and wrote the article.

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“…Other factors that stabilise MTs were shown to participate to spindle length control. This is the case of the chromokinesin Kid that bundles and stabilises MTs [Tokai‐Nishizumi et al., 2005; Bisht et al., 2019] and of other factors of the TOG‐like domain containing‐protein family CLASP/Mast/Orbit that act at the MT plus‐end to stabilise them [Maiato et al., 2005; Hannak and Heald, 2006; Laycock et al., 2006; Reis et al., 2009; Espiritu et al., 2012; Young et al., 2014], both of these families being in fact primarily important for spindle integrity. In addition, MT depolymerases or destabilisers, such as the Kinesin‐13 MCAK [Mitchison et al., 2005], the MT destabilising protein Stathmin/Op18 [Budde et al., 2001], and of various MT depolymerases of the Kinesin‐8 family [Savoian and Glover, 2010; Wang et al., 2010; Stout et al., 2011; Weaver et al., 2011] were also shown to be involved in spindle length control in particular in Xenopus and invertebrate systems.…”

Section: Molecular Control Of Spindle Length Through Modulation Of Mtmentioning

confidence: 99%

Mechanisms of spindle assembly and size control

Gibeaux

2020

Biology of the Cell

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The spindle is crucial for cell division by allowing the faithful segregation of replicated chromosomes to daughter cells. Proper segregation is ensured only if microtubules (MTs) and hundreds of other associated factors interact to assemble this complex structure with the appropriate architecture and size. In this review, we describe the latest view of spindle organisation as well as the molecular gradients and mechanisms underlying MT nucleation and spindle assembly. We then discuss the overlapping physical and molecular constraints that dictate spindle morphology, concluding with a focus on spindle size regulation.

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Induction of a Spindle-Assembly-Competent M Phase in Xenopus Egg Extracts

Cited by 5 publications

References 82 publications

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Mechanisms of spindle assembly and size control

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