The overall focus of our group is on gene regulatory control mechanisms underlying cell fate decisions during vertebrate embryogenesis. This is divided into two main areas:
Trophoblast Stem Cell (TSC) differentiation
TSCs are a multipotent cell type of foetal origin, which gives rise to the range of distinct trophoblasts subtypes within the placenta. Different trophoblast subtypes control different aspects of placenta function, such as maternal-foetal exchange, hormone production and expansion of the maternal vasculature to enhance the blood supply to the developing foetus. We culture and study mouse TSCs in the lab to investigate the molecular mechanisms controlling cell fate decisions during trophoblast differentiation using genetic, functional genomics, transcriptomics and proteomics approaches. This will help us to understand how the placenta develops correctly to maintain a healthy pregnancy, and how defects in placenta formation can lead to pregnancy complications such as preeclampsia.
Endoderm specification and differentiation
Endoderm, one of the three primary germ layers in the early vertebrate embryo makes direct contributions to several organs including liver, pancreas, and the digestive and respiratory tracts. A major goal of our research is to understand how gene regulatory networks control the specification of endoderm and its diversification into different endodermal cell types. To address this we use both zebrafish embryos and differentiating mouse embryonic stem cells as model systems, combined with genetic, functional genomic and transcriptomic approaches. Understanding how different endoderm cell types form during development will provide key insights into developmental disorders, and lead to refined regenerative medicine strategies.
PhD, Biology, Wellcome Trust Sanger Institute/University of Cambridge, 2009
BSc (Hons), Applied Biochemistry, University of Liverpool, 2004
Member of the British Society for Developmental Biology
- Osborn, Daniel P. S., Li, Kuoyu, Cutty, Stephen J., Nelson, A. C. (Andrew Christopher), Wardle, Fiona C., Hinits, Yaniv, Hughes, Simon M., 2020. Fgf-driven Tbx protein activities directly induce myf5 and myod to initiate zebrafish myogenesis. Development, 147 (8)
- Nelson, A. C. (Andrew Christopher), Mould, Arne W., Bikoff, Elizabeth K., Robertson, Elizabeth J., 2017. Mapping the chromatin landscape and Blimp1 transcriptional targets that regulate trophoblast differentiation. Scientific Reports, 7 (1)
- Nelson, A. C. (Andrew Christopher), Cutty, Stephen J., Gasiunas, Saule N, Deplae, Isabella, Stemple, Derek L., Wardle, Fiona C., 2017. In vivo regulation of the zebrafish endoderm progenitor niche by T-box transcription factors. Cell Reports, 19 (13), pp. 2782-2795
- Nelson, A. C., Mould, Arne W., Bikoff, Elizabeth K., Robertson, Elizabeth J., 2016. Single-cell RNA-seq reveals cell type-specific transcriptional signatures at the maternal-foetal interface during pregnancy. Nature Communications, 7
- Mould, Arne W., Morgan, Marc A. J., Nelson, A. C., Bikoff, Elizabeth K., Robertson, Elizabeth J., 2015. Blimp1/Prdm1 functions in opposition to Irf1 to maintain neonatal tolerance during postnatal intestinal maturation. PLoS Genetics, 11 (7)
- Windner, S. E., Doris, R. A., Ferguson, C. M., Nelson, A. C., Valentin, G., Tan, H., Oates, A. C., Wardle, F. C., Devoto, S. H., 2015. Tbx6, Mesp-b and Ripply1 regulate the onset of skeletal myogenesis in zebrafish. Development, 142 (6), pp. 1159-1168
- Nelson, A. C., Cutty, Stephen J, Niini, Marie, Stemple, Derek L., Flicek, Paul, Houart, Corinne, Bruce, Ashley E. E., Wardle, Fiona C., 2014. Global identification of Smad2 and Eomesodermin targets in zebrafish identifies a conserved transcriptional network in mesendoderm and a novel role for Eomesodermin in repression of ectodermal gene expression. BMC Biology, 12 (1)
- Nelson, A. C., Wardle, F. C., 2013. Conserved non-coding elements and cis regulation : actions speak louder than words. Development, 140 (7), pp. 1385-1395
- Bogani, D., Morgan, M. A. J., Nelson, A. C., Costello, I., McGouran, J. F., Kessler, B. M., Robertson, E. J., Bikoff, E. K., 2013. The PR/SET domain zinc finger protein Prdm4 regulates gene expression in embryonic stem cells but plays a nonessential role in the developing mouse embryo. Molecular and Cellular Biology, 33 (19), pp. 3936-3950
- Jahangiri, Leila, Nelson, A. C., Wardle, Fiona C., 2012. A cis-regulatory module upstream of deltaC regulated by Ntla and Tbx16 drives expression in the tailbud, presomitic mesoderm and somites. Developmental Biology, 371 (1), pp. 110-120
- Nelson, A. C., Pillay, Nischalan, Henderson, Stephen, Presneau, Nadège, Tirabosco, Roberto, Halai, Dina, Berisha, Fitim, Flicek, Paul, Stemple, Derek L., Stern, Claudio D., Wardle, Fiona C., Flanagan, Adrienne M., 2012. An integrated functional genomics approach identifies the regulatory network directed by brachyury (T) in chordoma. Journal of Pathology, 228 (3), pp. 274-285
- Ramani, A. K., Calarco, J. A., Pan, Q., Mavandadi, S., Wang, Y., Nelson, A. C., Lee, L. J., Morris, Q., Blencowe, B. J., Zhen, M., Fraser, A. G., 2011. Genome-wide analysis of alternative splicing in Caenorhabditis elegans. Genome Research, 21 (2), pp. 342-348
- Ramani, Arun K., Nelson, A. C., Kapranov, Philipp, Bell, Ian, Gingeras, Thomas R., Fraser, Andrew G., 2009. High resolution transcriptome maps for wild-type and nonsense-mediated decay-defective Caenorhabditis elegans. Genome Biology, 10 (9)
Title | Funder | Award start | Award end |
---|---|---|---|
Regulation of trophoblast differentiation by BAF complex chromatin remodelling factors | MRC | 01 May 2019 | 30 Nov 2022 |
CoA:Regulation of trophoblast differentiation by BAF complex chromatin remodelling factors; linked to Ideate 59571 | UK Research and Innovation | 01 Mar 2021 | 01 Sep 2021 |
Seed Award - Analysing the chromatin and transcriptional landscapes controlling endoderm cell fate decisions during zebrafish embryogenesis - supplement for 55562 | Wellcome Trust | 01 Sep 2020 | 28 Feb 2021 |
Seed Award - Analysing the chromatin and transcriptional landscapes controlling endoderm cell fate decisions during zebrafish embryogenesis | Wellcome Trust | 01 Mar 2018 | 31 Aug 2020 |