f0 f1 f2 - european federation of animal science · 2016. 10. 25. · milekic (gingrich), smith...
TRANSCRIPT
![Page 1: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/1.jpg)
Ancestral influences on descendant generations: a case study using the olfactory system in rodents
F0
F1
F2
Brian Dias, PhD.
Assistant Professor, Emory University School of Medicine
Department of Psychiatry and Behavioral Sciences
Yerkes National Primate Research Center
66th EAAP Annual Meeting: September 1, 2015 (Warsaw, Poland)
1
![Page 2: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/2.jpg)
2
Standing on the shoulders of helpful giants…
THANK YOU
• Kerry Ressler
• Yerkes Animal Care
• Michael deBelis, Carrie Bearden,
Jeremy Veenstra-VanderWeele
(Mentors at ACNP, SOBP)
• Mueller, Morgan, Rodgers, Bale
• Debiec, Sullivan, Francis Lee
• Milad (K & M), Graham
• Rick Richardson
• Russo, Dietz, Nestler
• Roth, Sweatt
• Tottenham
• Jovanovic
• Yehuda
• Meaney, Szyf
• Manusuy
• Axel, Buck, Mombaerts, Dulac, Anderson
• Kandel
• Rene Hen, McEwen
• LeDoux, Fanselow, Davis, Josselyn
• Quirk, Luthi, Andrew Holmes, Tye
2
Funding: HHMI, NIH Base Grant to Yerkes National Primate Research Center
![Page 3: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/3.jpg)
3
Social Media Statement
![Page 4: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/4.jpg)
4
Reality and Promises of Epigenetics for Animal Science
![Page 5: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/5.jpg)
5
Reality and Promises of Epigenetics for Animal Science
Dias et al, Trends in Neurosci (2015)
![Page 6: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/6.jpg)
6
Reality and Promises of Epigenetics for Animal Science
Reality
Unknowns
G x E Stressful experiences interact with the genome
Promises
Do positive environments interact with the genome
Manipulating gene expression in sperm and egg
![Page 7: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/7.jpg)
7
![Page 8: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/8.jpg)
8
G x E
![Page 9: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/9.jpg)
wtpotus.wordpress.com
9
Ancestral environments affect biology of descendants
![Page 10: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/10.jpg)
10
reachofclaycounty.org
Ancestral environments affect biology of descendants
![Page 11: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/11.jpg)
11
Ancestral environments affect biology of descendants
![Page 12: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/12.jpg)
How do descendants inherit information from ancestors?
12
![Page 13: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/13.jpg)
Nature, 2010
Cell, 2010
Information about ancestral nutritional environment can be inherited by descendants
13
![Page 14: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/14.jpg)
PNAS, 2007
F0 female rats exposed to fungicide – Mate preference affected in F3 generation
Biol Psychiatry, 2011
Social defeat of F0 male mice – F1 generation showed depression-like behavior
Ancestral environment prior to conception affects behavior of descendant generations
Also: Franklin (Mansuy), Roth (Sweatt), Rodgers (Bale) and others 14
![Page 15: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/15.jpg)
15
![Page 16: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/16.jpg)
Mammalian olfactory system
DeMaria & Ngai, 2010
All olfactory sensory neurons (OSNs) in the nose expressing a single odorant receptor, project to a discrete region called a glomerulus in the olfactory bulb. 16
![Page 17: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/17.jpg)
M71-LacZ transgenic mice M71 receptor (Olfr151) expressing neurons stained blue
MOE
Olfactory bulb
Acetophenone activates M71 OSNs (Bozza et al., 2002). Propanol does not.
Vassalli et al., 2002
17
![Page 18: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/18.jpg)
Test descendant generations
Mate
Condition F0 generation with Odor (Odor+Shock)
Odor + Footshock
18
How do descendants inherit information from ancestors?
![Page 19: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/19.jpg)
19
![Page 20: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/20.jpg)
Test descendant generations
Mate
Condition F0 generation with Odor (Odor+Shock)
Odor + Footshock
20
How do descendants inherit information from ancestors?
![Page 21: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/21.jpg)
Dias & Ressler, Nat Neurosci (2014)
F0 olfactory fear conditioning results in F1 generation being sensitive to F0 conditioned odor
21
n = 9-13
![Page 22: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/22.jpg)
Dias & Ressler, Nat Neurosci (2014)
F0 olfactory fear conditioning results in enhanced neuroanatomical representation in F1 generation
22
n = 18-38
![Page 23: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/23.jpg)
similac.com olympicjokes.com
Transmitted vs Inherited
Like Father – Like Son : How?
23
![Page 24: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/24.jpg)
Inheritance of structure and function
1. IVF
2. F2 generation 1. Cross-fostering
24
![Page 25: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/25.jpg)
M71 glomeruli in the olfactory bulbs of F1 males are larger when F0 conditioning occurs with Acetophenone (Offspring derived from F0-sperm via IVF)
Dias & Ressler, Nat Neurosci (2014)
25
n = 16-19
Thank you: Emory Transgenic Mouse Core
![Page 26: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/26.jpg)
Like Father – Like Son: Inherited BUT How?
olympicjokes.com
26
![Page 27: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/27.jpg)
ncc.go.jp
Epigenetic mechanisms may explain enhanced transcription of the M71 odorant receptor
27
![Page 28: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/28.jpg)
28 Dias & Ressler, Nat Neurosci (2014)
Olfr151 (M71) is hypo-methylated in sperm of F0-Ace males
n = 9
Thank you: Active Motif (especially Paul Labhart)
![Page 29: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/29.jpg)
Modified version from commentary by Moshe Syzf, Nat
Nat Neurosci (2014)
Inheritance of olfactory sensitivity & neuroanatomy from ancestral generation
29
![Page 30: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/30.jpg)
30
Reality and Promises of Epigenetics for Animal Science
Reality
Unknowns
G x E Stressful experiences interact with the genome
Promises
Do positive environments interact with the genome
Manipulating gene expression in sperm and egg
![Page 31: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/31.jpg)
31
What can we do with this information?
Dias & Ressler, Bioessays (2014)
Reik, Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith)
![Page 32: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/32.jpg)
32
1. Nose to gametes: Exosomes containing ncRNA (miRNA, piRNA, tRFs) Active project: Profiling circulating exosomes and sperm RNA (Commercial) 2. What is going on in the sperm: Focus on methylation Active project: Genome-wide 5hmC and 5mC analysis (Collab: Peng Jin)
Sources of information transfer in sperm
![Page 33: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/33.jpg)
33
Reality and Promises of Epigenetics for Animal Science
Reality
Unknowns
G x E Stressful experiences interact with the genome
Promises
Do positive environments interact with the genome
Manipulating gene expression in sperm and egg
![Page 34: F0 F1 F2 - European Federation of Animal Science · 2016. 10. 25. · Milekic (Gingrich), Smith (Mill), Radford (Ferguson-Smith) 32 1. Nose to gametes: Exosomes containing ncRNA (miRNA,](https://reader033.vdocuments.net/reader033/viewer/2022061004/60b2e3da867fce736e3956e6/html5/thumbnails/34.jpg)
34
Reality and Promises of Epigenetics for Animal Science
Reality
Unknowns
G x E Stressful experiences interact with the genome
Promises
Do positive environments interact with the genome
Manipulating gene expression in sperm and egg