Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation in vivo. Olivera-Martinez, I., Schurch, N., Li, R. A., Song, J., Halley, P. A., Das, R. M., Burt, D. W., Barton, G. J., & Storey, K. G. Development (Cambridge, England), 141(16):3266–3276, August, 2014.
doi  abstract   bibtex   
Here, we exploit the spatial separation of temporal events of neural differentiation in the elongating chick body axis to provide the first analysis of transcriptome change in progressively more differentiated neural cell populations in vivo. Microarray data, validated against direct RNA sequencing, identified: (1) a gene cohort characteristic of the multi-potent stem zone epiblast, which contains neuro-mesodermal progenitors that progressively generate the spinal cord; (2) a major transcriptome re-organisation as cells then adopt a neural fate; and (3) increasing diversity as neural patterning and neuron production begin. Focussing on the transition from multi-potent to neural state cells, we capture changes in major signalling pathways, uncover novel Wnt and Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid biogenesis and TGFβ). This analysis further predicts changes in cellular processes, cell cycle, RNA-processing and protein turnover as cells acquire neural fate. We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase. This latter step may provide time for epigenetic events to mediate large-scale transcriptome re-organisation; consistent with this, we uncover simultaneous downregulation of major chromatin modifiers as the neural programme is established. We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation. Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.
@article{olivera-martinez_major_2014,
	title = {Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation in vivo},
	volume = {141},
	issn = {1477-9129},
	doi = {10.1242/dev.112623},
	abstract = {Here, we exploit the spatial separation of temporal events of neural differentiation in the elongating chick body axis to provide the first analysis of transcriptome change in progressively more differentiated neural cell populations in vivo. Microarray data, validated against direct RNA sequencing, identified: (1) a gene cohort characteristic of the multi-potent stem zone epiblast, which contains neuro-mesodermal progenitors that progressively generate the spinal cord; (2) a major transcriptome re-organisation as cells then adopt a neural fate; and (3) increasing diversity as neural patterning and neuron production begin. Focussing on the transition from multi-potent to neural state cells, we capture changes in major signalling pathways, uncover novel Wnt and Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid biogenesis and TGFβ). This analysis further predicts changes in cellular processes, cell cycle, RNA-processing and protein turnover as cells acquire neural fate. We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase. This latter step may provide time for epigenetic events to mediate large-scale transcriptome re-organisation; consistent with this, we uncover simultaneous downregulation of major chromatin modifiers as the neural programme is established. We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation. Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.},
	language = {eng},
	number = {16},
	journal = {Development (Cambridge, England)},
	author = {Olivera-Martinez, Isabel and Schurch, Nick and Li, Roman A. and Song, Junfang and Halley, Pamela A. and Das, Raman M. and Burt, Dave W. and Barton, Geoffrey J. and Storey, Kate G.},
	month = aug,
	year = {2014},
	pmid = {25063452},
	pmcid = {PMC4197544},
	keywords = {Animals, Body Patterning, Cell Cycle, Cell Differentiation, Cell Lineage, Chick Embryo, Chromatin, DAG, Developmental, Epigenesis, Fibroblast Growth Factors, Gene Expression Regulation, Genetic, Histone Deacetylase 1, Mice, Neurogenesis, Neurons, Oligonucleotide Array Sequence Analysis, RNA, Sequence Analysis, Signal Transduction, Spinal Cord, Time Factors, Transforming Growth Factor beta, transcriptome},
	pages = {3266--3276}
}
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