Over twenty years ago, somatic cell nuclear transfer (SCNT) let scientists successfully clone the first mammal—Dolly the sheep. Despite advances since then, the efficiency of this process remains low. In the July issue of G3, Srirattana and St. John report a method to deplete cattle donor cells of mitochondrial DNA and efficiently generate blastocysts from these depleted donors.
In SCNT, a nucleus taken from a mature, differentiated somatic donor cell is placed into an oocyte whose nucleus has been removed. Together, this newly created cell goes on to form an embryo whose nuclear genome is identical to the donor cell’s. The low efficiency of SCNT is thought to be partially due to incomplete epigenetic reprogramming of the new embryo. In fact, treatment of embryos with the histone deacetylase inhibitor trichostatin A (TSA) is widely used to enhance SCNT in mouse.
Nuclear DNA isn’t the only genetic information in the cell, though. Mitochondria house a distinct genome that is maternally inherited, and mitochondrial DNA (mtDNA) from donor cells can be randomly transmitted from the donor cell to the embryo. The mixing of mtDNA from the two initial cells complicates the process of SCNT.
Normally, an organism inherits its mtDNA from its mother, but SCNT embryos have two different sets of mtDNA—donor cell and oocyte—to deal with, and the interplay between the two can cause genomic instability, aneuploidy, poor embryo quality and implantation rates, and metabolic defects.
To combat this problem, Srirattana and St. John depleted the mtDNA from cattle donor cells by using 2’,3’-dideoxycytidine (ddC), which inhibits the mtDNA-specific DNA polymerase gamma but doesn’t affect nuclear DNA. They compared embryos made from mtDNA-depleted cells to nondepleted cells, and they looked at the effect of TSA treatment on both depleted and nondepleted cells.
They found that mtDNA-depleted donor cells can generate viable blastocysts that contain only oocyte mtDNA—as is the case in blastocysts formed by sperm fertilization. Donors depleted of mtDNA had a lower rate of blastocyst generation than nondepleted cells, but the use of TSA brought the blastocyst rate back to that of nondepleted donors. Srirattana and St. John also showed that gene expression differed between blastocysts created from depleted and nondepleted cells; they found that differentially expressed genes were largely involved in embryonic development, suggesting the use of mtDNA-depleted donor cells can alter development of the cloned embryos.
This work demonstrates that depleting mtDNA from donor cells is an effective tool for creating SCNT embryos with mitochondrial genomes inherited only from the oocyte. Such embryos will hopefully avoid some of the problems created by mixing incompatible mitochondrial genomes and may one day make SCNT easier and more efficient for cattle scientists and others who rely on this cloning technique.
CITATION:
Manipulating the Mitochondrial Genome To Enhance Cattle Embryo Development
Kanokwan Srirattana, Justin C. St. John
G3: Genes, Genomes, Genetics July 2017 7: 2065-2080;
https://doi.org/10.1534/g3.117.042655
http://www.g3journal.org/content/7/7/2065
Scientific Editor and Programs Manager. Genetics and Molecular Biology PhD. Find me on Twitter: @_sbay
View all posts by Sarah Bay »Read more in
-
Hongyu Zhao joins GENETICS as new Senior Editor
A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team. Hongyu ZhaoSenior Editor Hongyu Zhao is the Ira V. Hiscock Professor of Biostatistics, Professor of Genetics, and Professor of Statistics and Data Science at Yale University. He received his BS in…
-
GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024
“At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…
-
In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation
Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…
-
Congratulations to the #Fungal24 Poster Award winners!
We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…
-
Poster presentation tips for TAGC 2024
You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…
-
Maximize your TAGC 2024 experience
A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…
-
Early Career Leadership Spotlight: Sarah Petrosky
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…
-
TAGC 2024 Early Career Award Winners
GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024. Don’t miss the opportunity…
-
Preeminent geneticists recognized with revamped GSA Awards
In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…
-
Fly Board funds outreach programs to spread the word about Drosophila research
In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…
-
New members of the GSA Board of Directors: 2024–2026
We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…