CytoCensus: mapping cell identity and division in tissues and organs using machine learning

Hailstone, Martin; Waithe, Dominic; Samuels, Tamsin J; Lu, Yang; Costello, Ita; Arava, Yoav; Robertson, Elizabeth J.; Parton, Richard M.; Davis, Ilan

doi:10.1101/137406

Cited by 8 publications

(9 citation statements)

References 70 publications

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“…The number of progeny was increased 1.4-fold in the Imp overexpressing brains and increased 1.6-fold in the syp RNAi brains compared to wild type. This phenotype is consistent with the increased proliferation rate previously observed in syp knockdown brains with ex vivo culture and live imaging (Hailstone et al, 2019). However…”

Section: Imp Promotes Nb Growth and Divisionsupporting

confidence: 91%

“…Individual NBs produce unique lineages of neurons (Pereanu and Hartenstein, 2006), with characteristically different clone sizes (Yu et al, 2013). Individual NBs also have differing division frequencies (Hailstone et al, 2019) and terminate division at different times (NB decommissioning) . This individual control ensures that the appropriate number of each neuron type is produced in the correct location during the construction of the brain.…”

Section: Introductionmentioning

confidence: 99%

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Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

Samuels

Järvelin

Ish‐Horowicz

et al. 2019

Preprint

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The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by known extrinsic signals. However, the intrinsic mechanisms that control the characteristic proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, while heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.

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Section: Imp Promotes Nb Growth and Divisionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

Samuels

Järvelin

Ish‐Horowicz

et al. 2019

Preprint

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“…Whole brains were dissected from 3 rd instar larvae in Schneider’s medium and cultured according to an improved protocol for long term culturing and imaging of larval brains (Cabernard and Doe, 2013; Hailstone et al, 2017). Live imaging was performed for 26 hr in an inverted Olympus FV1200 confocal microscope (Ilan Davis Group, Department of Biochemistry, University of Oxford).…”

Section: Methodsmentioning

confidence: 99%

Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

Zacharioudaki

Falo‐Sanjuan

Bray

2019

eLife

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To progress towards differentiation, progeny of stem cells need to extinguish expression of stem-cell maintenance genes. Failures in such mechanisms can drive tumorigenesis. In Drosophila neural stem cell (NSC) lineages, excessive Notch signalling results in supernumerary NSCs causing hyperplasia. However, onset of hyperplasia is considerably delayed implying there are mechanisms that resist the mitogenic signal. Monitoring the live expression of a Notch target gene, E(spl)mγ, revealed that normal attenuation is still initiated in the presence of excess Notch activity so that re-emergence of NSC properties occurs only in older progeny. Screening for factors responsible, we found that depletion of Mi-2/NuRD ATP remodeling complex dramatically enhanced Notch-induced hyperplasia. Under these conditions, E(spl)mγ was no longer extinguished in NSC progeny. We propose that Mi-2 is required for decommissioning stem-cell enhancers in their progeny, enabling the switch towards more differentiated fates and rendering them insensitive to mitogenic factors such as Notch.

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“…The speed of NB division is also a parameter molecularly controlled that could impact the number of cells produced by a lineage. The average speed of NB divisions in the larvae is around 80-90 mins per division (Hailstone et al, 2020;Homem et al, 2013), however this speed varies from NB to NB (Hailstone et al, 2020). The heterogeneity of NB division speed seems also to be regulated by the opposite temporal gradient of Imp and Syp in the NB.…”

Section: Introductionmentioning

confidence: 96%

The role of Imp and Syp RBPs in precise neuronal elimination by apoptosis through the regulation of TFs

Guan

Bouchet

Darmas

et al. 2021

Preprint

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SUMMARYNeuronal stem cells produce a finite and stereotyped number of neuronal progenies. This process must be finely regulated during development and adult stages to ensure proper brain function. In Drosophila, stem cells, called Neuroblasts, produce an invariant number of neurons. Two RNA binding proteins, Imp and Syp, play a central role in controlling the speed of division and the end of the proliferative phase of individual NBs, two parameters that influences the final number of neurons produced. Here, we have discovered a novel function for Imp and Syp, where both RBPs also shape the number of neurons produced by a stem cell by controlling program cell death (PCD) in immature neurons. By studying a neuroblast lineage, called Lin A/15, which produces motoneurons (MNs) and glia, we have demonstrated that Lin A/15 stem cell spends 40% of its time producing immature MNs which are eliminated by apoptosis. We have revealed that only the first born MNs (Imp +) survive while the last born MNs (Imp-Syp+) are eliminated by apoptosis. Both RBPs play a central role in neuronal survival, Imp promotes neuronal survival while Syp promotes cell death in immature motoneurons. Interestingly their opposite temporal gradient in Lin A/15 stem cell also determines the end of Lin A/15 stem cell neurogenesis by PCD. Both RNA binding proteins are conserved in vertebrates and seem to play a central role in the number of neurons produce during development. The Drosophila model and its genetic tools offer a unique chance to decipher their function in neural stem cell versus immature neurons.

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CytoCensus: mapping cell identity and division in tissues and organs using machine learning

Cited by 8 publications

References 70 publications

Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

The role of Imp and Syp RBPs in precise neuronal elimination by apoptosis through the regulation of TFs

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