Samuel Heron

Samuel Heron


Research Interests

I am currently investigating neuron-astrocyte signaling processes using bioinformatic network analysis in addition to broader machine learning and systems biology methods. Previous experimentation has produced cultures of neurons from stem cells, with recent studies demonstrating increased differentiation, maturation and synaptogenesis when co-cultured with astrocytes. Through use of co-culture data using neurons of one species and astrocytes of another (mouse, rat or human) I will separate, by species and thus by cell, and analyse RNA-Seq and epigenetic data to explore and identify signaling processes between the cell types with the hope of identifying the source of the beneficial developmental effects observed in co-culture.

Publications:
2017
  Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism
Hasel, P, Dando, O, Jiwaji, Z, Baxter, P, Todd, AC, Heron, S, Márkus, NM, Mcqueen, J, Hampton, DW, Torvell, M, Tiwari, SS, Mckay, S, Eraso-pichot, A, Zorzano, A, Masgrau, R, Galea, E, Chandran, S, Wyllie, DJA, Simpson, TI & Hardingham, GE 2017, 'Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism' Nature Communications, vol 8, 15132, pp. 1-17. DOI: 10.1038/ncomms15132
The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte–neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte–neuron metabolic cooperation.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Hasel, Philip, Dando, Owen, Jiwaji, Zoeb, Baxter, Paul, Todd, Alison C., Heron, Samuel, Márkus, Nóra M., Mcqueen, Jamie, Hampton, David W., Torvell, Megan, Tiwari, Sachin S., Mckay, Sean, Eraso-pichot, Abel, Zorzano, Antonio, Masgrau, Roser, Galea, Elena, Chandran, Siddharthan, Wyllie, David J. A., Simpson, T. Ian & Hardingham, Giles E..
Number of pages: 17
Pages: 1-17
Publication Date: 2 May 2017
Publication Information
Category: Article
Journal: Nature Communications
Volume: 8
ISSN: 2041-1723
Original Language: English
DOIs: 10.1038/ncomms15132
2016
  Separation of mixed source RNA-Seq reads by comparative genomic processing
Heron, S, Dando, O, Hardingham, G & Simpson, TI 2016, 'Separation of mixed source RNA-Seq reads by comparative genomic processing' 15th European Conference on Computational Biology (ECCB) 2016 , The Hague, Netherlands, 3/09/16 - 7/09/16, . DOI: 10.7490/f1000research.1113126.1
Knowledge of the cell-autonomous and non-autonomous mechanisms operating within biological systems is essential to reveal the underlying molecular processes at work and is particularly important in functional studies of neurological diseases and cancers. These studies commonly measure gene expression levels in different cell types, but are often confounded by invasive sample processing. Indeed physical separation techniques for cell mixtures have been shown to trigger stress and apoptosis related genes, obscuring the identification of genes of interest and introducing bias. We present a novel approach that alleviates this issue for gene expression quantification using RNA-seq by conducting in silico sequence separation between different sources. Our method takes sequences from mixed species RNA-seq samples (for example two cell types each belonging to closely related species, or different strains of the same species) and differentially maps them between the two genomes. The mappings for each read are then assessed by alignment quality factors and assigned to one source genome or the other according to tuneable selection criteria. Separated read sets can then be examined using standard quantification and differential expression methods for RNA-seq data. Using simulated and real data for rat and mouse we demonstrate here that reads from closely related species can be successfully separated in this manner.
General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Heron, Samuel, Dando, Owen, Hardingham, Giles & Simpson, T. Ian.
Keywords: (Comparative genomics, genomics, RNA-seq. )
Publication Date: 12 Sep 2016
Publication Information
Category: Poster
Original Language: English
DOIs: 10.7490/f1000research.1113126.1
  Expression of mRNA Encoding Mcu and Other Mitochondrial Calcium Regulatory Genes Depends on Cell Type, Neuronal Subtype, and Ca2+ Signaling
Márkus, NM, Hasel, P, Qiu, J, Bell, KFS, Heron, S, Kind, PC, Dando, O, Simpson, TI & Hardingham, GE 2016, 'Expression of mRNA Encoding Mcu and Other Mitochondrial Calcium Regulatory Genes Depends on Cell Type, Neuronal Subtype, and Ca2+ Signaling' PLoS One, vol 11, no. 2, pp. e0148164. DOI: 10.1371/journal.pone.0148164

Uptake of Ca2+ into the mitochondrial matrix controls cellular metabolism and survival-death pathways. Several genes are implicated in controlling mitochondrial Ca2+ uptake (mitochondrial calcium regulatory genes, MCRGs), however, less is known about the factors which influence their expression level. Here we have compared MCRG mRNA expression, in neural cells of differing type (cortical neurons vs. astrocytes), differing neuronal subtype (CA3 vs. CA1 hippocampus) and in response to Ca2+ influx, using a combination of qPCR and RNA-seq analysis. Of note, we find that the Mcu-regulating Micu gene family profile differs substantially between neurons and astrocytes, while expression of Mcu itself is markedly different between CA3 and CA1 regions in the adult hippocampus. Moreover, dynamic control of MCRG mRNA expression in response to membrane depolarization-induced Ca2+ influx is also apparent, resulting in repression of Letm1, as well as Mcu. Thus, the mRNA expression profile of MCRGs is not fixed, which may cause differences in the coupling between cytoplasmic and mitochondrial Ca2+, as well as diversity of mitochondrial Ca2+ uptake mechanisms.


General Information
Organisations: Edinburgh Imaging Facilities.
Authors: Márkus, Nóra M, Hasel, Philip, Qiu, Jing, Bell, Karen F S, Heron, Samuel, Kind, Peter C, Dando, Owen, Simpson, T Ian & Hardingham, Giles E.
Pages: e0148164
Publication Date: 2 Feb 2016
Publication Information
Category: Article
Journal: PLoS One
Volume: 11
Issue number: 2
ISSN: 1932-6203
Original Language: English
DOIs: 10.1371/journal.pone.0148164
2015
  Multi-species integration of miRNA binding site data to improve target prediction accuracy for synaptic miRNAs
Heron, S & Simpson, TI 2015, 'Multi-species integration of miRNA binding site data to improve target prediction accuracy for synaptic miRNAs' 23rd Annual International Conference on Intelligent Systems for Molecular Biology and the 14th European Conference on Computational Biology 2015, Dublin, Ireland, 10/07/14 - 14/07/14, .
Micro-RNAs (miRNA) are thought to play an important role in the modulation of synaptic strength during activity dependent synaptic plasticity by regulating protein synthesis. Identifying the target mRNAs of the miRNAs involved is a crucial part of understanding how this regulation takes place, but is confounded by the small size and sequence variability of miRNA binding sites (typically as few as 6-8 nucleotides). Recent studies have attempted to improve the identification of miRNA targets by isolating miRNAs and their mRNA targets as part of the RISC complex using antibodies raised against the Arg2 protein in both human and mice and sequencing the resulting RNA pools. We used data produced by this technique, in addition to other cross-species information, to produce a classification procedure for improving microRNA target prediction in the rat.
General Information
Organisations: Edinburgh Neuroscience.
Authors: Heron, Samuel & Simpson, T. Ian.
Publication Date: 23 Jul 2015
Publication Information
Category: Poster
Original Language: English

Projects:
Understanding Neuron-Astrocyte Signaling: Co-culture of astrocytes with neurons improves development and maturation rates through transcriptomic and epigenetic change (PhD)