STEM CELL GENETICS LAB
RESEARCH
Stem Cell Genetics Lab, Professor Ivana Barbaric
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We are the Stem Cell Genetics Lab—a team of biologists and computational thinkers tackling the challenges of stem cell genetics. Whether we are modelling genetic diseases or exploring the frontiers of early development, our mission is to understand how genetic variation influences cellular fate and behaviour. We believe that by mastering the genetics of the "starting cell," we can unlock the full potential of stem cell technology.
GENETIC CHANGES IN STEM CELLS
DISEASE MODELLING USING STEM CELLS
STEM CELL FATEÂ CONTROL
Lab members
Stem Cell Genetics Lab
FORMER MEMBERS
Dr Joanne Lacey Postdoctoral Researcher
Dr Dylan Stavish Postdoctoral Researcher
Dr Christopher Price PhD student, Postdoctoral Researcher
Dr Rebecca Lea Postdoctoral Researcher
Dr Theo Wing PhD student, Postdoctoral Researcher
Larissa Butler PhD student
Bethany James PhD student
Chiara Sander Research Assistant
Antigoni Gogolou Research Assistant
Nicholas Brown Research Assistant
SELECTED RECENT PUBLICATIONS
For a full list see: https://pubmed.ncbi.nlm.nih.gov/?sort=date&term=barbaric+i&sort_order=desc
A call to action for deciphering genetic variants in human pluripotent stem cells for cell therapy
Human pluripotent stem cell (hPSC)-based therapies offer promise but pose potential risks due to culture-acquired genetic variants, some of which have been linked with cancer. An international workshop addressed these concerns, highlighting the need for improved strategies to stratify variants and chart a path toward definitive guidelines in hPSC-based therapy.
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GENETICALLY VARIANT HUMAN PLURIPOTENT STEM CELLS SELECTIVELY ELIMINATE WILD-TYPE COUNTERPARTS THROUGH YAP-MEDIATED CELL COMPETITION
Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.
https://pubmed.ncbi.nlm.nih.gov/38964325/
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The appearance of genetic changes in human pluripotent stem cells (hPSCs) presents a concern for their use in research and regenerative medicine. Variant hPSCs that harbor recurrent culture-acquired aneuploidies display growth advantages over wild-type diploid cells, but the mechanisms that yield a drift from predominantly wild-type to variant cell populations remain poorly understood. Here, we show that the dominance of variant clones in mosaic cultures is enhanced through competitive interactions that result in the elimination of wild-type cells. This elimination occurs through corralling and mechanical compression by faster-growing variants, causing a redistribution of F-actin and sequestration of yes-associated protein (YAP) in the cytoplasm that induces apoptosis in wild-type cells. YAP overexpression or promotion of YAP nuclear localization in wild-type cells alleviates their "loser" phenotype. Our results demonstrate that hPSC fate is coupled to mechanical cues imposed by neighboring cells and reveal that hijacking this mechanism allows variants to achieve clonal dominance in cultures.
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doi: 10.1016/j.devcel.2021.07.019
PLACEMENTS
As a Year 12 Sixth Form student looking to study Biomedical Science at university, stem cell biology is a field that I find especially interesting. I wanted to expand my knowledge of stem cells and gain familiarity within a lab setting. I was given the opportunity to do some work experience for a week in Ivana’s lab, where I had the incredible chance to immerse myself in the ongoing stem cell research.
During my time in the lab, I learnt the importance of working in a sterile environment and shadowed PhD students undertaking their individual research projects.
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Throughout the week I had the invaluable opportunity to work with hPSCs myself. I learnt how to work in a biosafety cabinet, how to perform media changes on stem cell cultures, coat a new flask ready for passaging and finally passaging stem cells. The hands on experience has taught me new skills such as aseptic technique and deepened my understanding of stem cell biology.
I thoroughly enjoyed my time in lab and I am grateful for the incredible opportunity.
Lauren H., Work Experience Student
Nina's Outreach Video: Extracting DNA from strawberries
For budding scientists and their teachers/ parents/ carers: have a go at extracting the DNA in your home- or school-based lab following the instructions in this video.
CONTACT DETAILS
Centre for Stem Cell Biology,
School of Biological Sciences
The University of Sheffield
Alfred Denny Building,
Sheffield, S10 2TN,
United Kingdom