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Developmental stem cell programming in livestock

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Current Research Interests

My research interests lie in the areas of Stem Cell biology and Reproductive Biology in large animal species. I am interested in these species both from a veterinary perspective and as disease models.

Research Interests

The main research themes in the laboratory are currently:

1. Muscle and adipose stem cell biology in livestock. We seek to gain a greater understanding of muscle and adipose stem cells in pigs and cattle, both in the context of cellular agriculture applications, and to elucidate molecular drivers of meat production in vivo. Within the latter aim, we are particularly interested on the mechanisms underlying programming of tissue stem cells by the pre-natal environment, and how this affects life-long health and productivity, using intrauterine growth restriction (IUGR) in pigs as a model. We are currently addressing these questions through studies seeking to characterise cell heterogeneity within muscle and adipose stem cell populations, as well as identifying molecular markers defining different cell subpopulations both in vivo and in vitro, in collaboration with industrial partners. We are also interested in identifying transcriptional and epigenetic signatures underlying cell fate decisions during tissue development in the context of IUGR or other pre-natal influences.

Cortes-Araya Y, Stenhouse C, Salavati M, Dan-Jumbo SO, Ho W, Ashworth CJ, Clark E, Esteves CL, Donadeu FX. KLB dysregulation mediates disrupted muscle development in intrauterine growth restriction. J Physiol. 2022 Apr;600(7):1771-1790

Salavati M, Woolley SA, Cortés Araya Y, Halstead MM, Stenhouse C, Johnsson M, Ashworth CJ, Archibald AL, Donadeu FX, Hassan MA, Clark EL. Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions. G3 (Bethesda). 2022 Feb 4;12(2):jkab424.

Weatherall EL, Avilkina V,Cortes-Araya Y, Dan-Jumbo S, Stenhouse C, Donadeu FX, Esteves CL. Differentiation Potential of Mesenchymal Stem/Stromal Cells Is Altered by Intrauterine Growth Restriction. Front vet Sci 2020, 7:558905

 

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.  In collaboration with different industry partners, current studies are aimed at developing applications of animal iPSCs in 1) veterinary regenerative medicine and 2) cellular agriculture 

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

Amilon KR, Cortes-Araya Y, Moore B, Lee S, Lillico S, Breton A, Esteves CL, Donadeu FX. Generation of functional myocytes from equine iPSCs. Cell Reprogramming. 2018 Oct;20(5):275-281. 

 

3. microRNA biology and diagnostic applications 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. 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. 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 J, Sánchez-Molano E, Psifidi A, DonadeuFX, Banos G. Association of plasma microRNA expression with age, genetic background and functional traits in dairy cattle. Sci Rep. 2018;8(1):12955

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.

 

  

Biography

Xavier Donadeu is a Full Professor and Divisional Head (Translational Bioscience) at The Roslin Institute and Royal (Dick) School of Veterinary Studies of The University of Edinburgh. He received a degree in Veterinary Medicine from Universitat Autonoma de Barcelona (1993), a Master of Science degree in Reproductive Physiology from Louisiana State University (1997) and a doctorate in Reproductive Physiology and Endocrinology from the University of Wisconsin (2002). From 2002 to 2005 he held a postdoctoral research position at the Carver College of Medicine of the University of Iowa.

Dr. Donadeu took up his faculty position in the School of Veterinary Studies of the University of Edinburgh in 2005 and was appointed Group Leader at The Roslin Institute in 2007. He is currently co-Editor-in-Chief for Domestic Animal Endocrinology, Associate Editor for PLoS One, and Associate Editor for Frontiers in Veterinary Science (Regenerative Medicine section). He is a Fellow of the Royal Society of Biologists, and has held different positions as scientific advisor for the Animal Health industry, and acted as FAO/IAEA consultant.   

His current scientific interests lie in the areas of 1) muscle and adipose stem cell biology in livestock, particularly their applications in cellular agriculture, and 2) miRNA biology and application as diagnostic biomarkers in veterinary species. Among other achievements, Dr. Donadeu's group has played key roles in the generation, characterisation and biomedical translation of induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) from veterinary species. and the discovery of miRNA biomarkers in livestock,

Education/Academic qualification

Endocrinology/Reproductive Physiology, Doctor of Science, University of Wisconsin–Madison

2002 → …

Award Date: 20 Dec 2002

Reproductive Physiology, Master in Science, Louisiana State Univ, Louisiana State University

1997 → …

Award Date: 29 Aug 1997

External positions

Scientific Advisor, Vetsina Animal Diagnostics Ltd.

2 Sep 2020 → …

Editor-in-Chief, Domestic Animal Endocrinology

1 Jun 2020 → …

Associate Editor, PLoS One

3 Jan 2018 → …

Associate Editor, Frontiers in Veterinary Science

3 Apr 2016 → …

Post-doctoral scholar, University of Iowa

Jan 2003Apr 2005

Clinical scholar, Louisiana State Univ, Louisiana State University

Jun 1994Apr 1995

Veterinary practitioner in Barcelona

Sep 1993May 1994

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