The Roslin Institute
The main research themes in the laboratory are currently:
1. microRNA biomarkers in livestock. MiRNAs are key global post-transcriptional regulators of tissue growth and differentiation both in health and disease. Because of their stability in body fluids, miRNAs have considerable potential as biomarkers of tissue function and are already being used as diagnostic biomarkers of human disease. Through genome-wide analyses in ovarian tissues we have identified miRNA signatures associated with different stages of follicle and luteal development in several large animal species (McBride et al., 2012; Schauer et al., 2013; Sontakke et al., 2014). Moreover, together with collaborators at the Edinburgh’s Centre for Reproductive Health we have taken a “One-health” approach by studying miRNA regulation of ovarian function in both cattle and humans. Our work identified a subset of miRNAs that are critical for luteal survival and function, thus identifying potentially new targets for infertility treatments (Mohammed et al., 2017). Current work in the laboratory aims to identify relevant miRNAs in circulation that could be used to monitor reproductive efficiency and predict life-long health and productivity in livestock, and we have already identified potential biomarkers of early pregnancy (Ioannidis and Donadeu, 2016a, 2017) and estrus (Ioannidis and Donadeu, 2016b).
McBride, D., Carre, W., Sontakke, S., Hogg, C. O., Law, A. S., Donadeu, F. X. & Clinton, M. 2012. Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary.Reproduction; 144(2):221-233
Schauer SN, Sontakke SD, Watson ED, Esteves CL, Donadeu FX. Involvement of miRNAs in equine follicle development. Reproduction. 2013; 146(3):273-282
Sontakke SD, Mohammed BT, McNeilly AS, Donadeu FX. Characterization of microRNAs differentially expressed during bovine follicle development. Reproduction. 2014; 148(3):271-283
Mohammed BT, Sontakke SD, Ioannidis J, Duncan WC, Donadeu FX. The adequate corpus luteum: miR-96 regulates luteal cell survival and progesterone production. J Clin Endocrinol Metab. 2017 Mar 20. doi: 10.1210/jc.2017-00259
Ioannidis J, Donadeu FX. Circulating miRNA signatures of early pregnancy in cattle. BMC Genomics. 2016a;17(1):184
Ioannidis J, Donadeu FX. Circulating microRNA Profiles during the Bovine Oestrous Cycle. PLoS One. 2016b;11(6):e0158160
Ioannidis J, Donadeu FX. Changes in circulating microRNA levels can be identified as early as day 8 of pregnancy in cattle. PLoS One 2017 Apr 5;12(4):e0174892.
2. Induced pluripotent stem cells (iPSCs) for Animal Health. iPSCs are obtained by in vitro reprogramming differentiated cells into embryo stem-like cells. Through their ability to differentiate virtually into any body tissue, iPSCs have revolutionised human biomedicine by providing an unparalleled platform to model and understand disease in vitro, as well as offering exciting prospects in clinical tissue regeneration. Similar potential, although so far much less explored, exists for iPSCs in veterinary medicine and the improvement of farm animal production. My laboratory has successfully generated iPSCs from horses and cattle and shown for the first time their ability to generate clinically- and production-relevant functional cell types (Breton et al., 2013; Sharma et al., 2014; Cravero et al., 2015). Current studies are aimed at the use of iPSCs in combination with gene editing technologies to 1) understand muscle development and disease and 2) elucidate genetic determinants of disease resistance in farm animal species.
Breton, A., Sharma, R., Diaz, A. C., Parham, A. G., Graham, A., Neil, C., Whitelaw, C. B., Milne, E. & Donadeu, F. X. 2013. Derivation and Characterization of Induced Pluripotent Stem Cells from Equine Fibroblasts. Stem Cells and Development; 22(4):611-621.
Sharma R, Livesey MR, Wyllie DJ, Proudfoot C, Whitelaw CB, Hay DC, Donadeu FX. Generation of functional neurons from feeder-free, keratinocyte-derived equine induced pluripotent stem cells. Stem Cells and Development. 2014; 23(13):1524-1534
Cravero D, Martignani E, Miretti S, Accornero P, Pauciullo A, Sharma R, Donadeu FX, Baratta M. Generation of induced pluripotent stem cells from bovine epithelial cells and partial redirection toward a mammary phenotype in vitro. Cellular Reprogramming. 2015; 17(3):211-220
3. Developmental programming of stem cells. Intrauterine growth restriction (IUGR) can occur in both humans and farm species, and is associated with small birth weight, poor neonatal survival and metabolic disease during adulthood. IUGR has a particularly high incidence in pigs due to continuous selection of sows for high prolificacy. A key feature of IUGR is reduced muscle development and increased body fat deposition after birth leading to poor growth and suboptimal carcass quality. We are using this as a naturally occurring, genetically controlled model to study the mechanisms determining progenitor cell fate during muscle and adipose tissue development in livestock. Our objectives are 1) using our expertise in the isolation of native mesenchymal progenitor populations from animal tissues (Esteves et al., 2017), to identify and isolate fetal myogenic and adipogenic precursor cells in pigs and 2) to identify transcriptomic and epigenomic signatures in progenitor cell populations associated with IUGR, which will provide novel information on the molecular determinants of stem cell proliferation and differentiation in the muscle of livestock
Esteves CL, Sheldrake TA, Mesquita SP, Pesántez JJ, Menghini T, Dawson L, Peault B, Donadeu FX. Isolation and characterization of equine native MSC subpopulations. Stem Cell Res Ther. 2017 Apr 18;8(1):80