Silva Lab
Reprogramming cells to develop embryo models
Embryo models will deliver high quality cells that will enable medical applications
For many years, our lab has focused on understanding the biology of nuclear reprogramming, with the ultimate goal of using generated induced pluripotent stem cells (iPSCs) for medical applications. Despite significant efforts by labs worldwide, approaches like pluripotent stem cell differentiation, direct/forward programming, and cell transdifferentiation have not yielded cell products with the desired molecular identities and physiological properties. We understand that during development, cells establish stage-specific epigenetic signatures that influence transcriptional profiles and phenotypes. These are influenced by the specific context which include the precise signalling cues present during development, which cannot be replicated by traditional pluripotent stem cell differentiation methods.
Thanks to the pioneering work of Magdalena Zernicka-Goetz and Alfonso Martinez-Arias, we now know that cells can self-organise and mimic aspects of embryonic development in vitro in a self-directed manner. Leveraging on our expertise in reprogramming, we hypothesise that creating embryo founder-like cells, as opposed to mixing different cell types, will allow us to generate more accurate and advanced embryo models.
We use pluripotent stem cells (Embryonic stem cells or induced pluripotent stem cells) as the starting material to reprogram these into embryo founder-like cells (Li et al, 2023; Guo et al 2024; Li et al, 2024). Embryo founder-like cells are novel in vitro cells resembling earlier stages of embryo development compared to ESCs. They express antagonistic factors such as Nanog, Gata6, Cdx2, and Oct4 and are poised to specify all blastocyst-like fates: trophectoderm/trophoblast, Primitive endoderm/Hypoblast and Naive Epiblast fates. The specified cells self-assemble into embryo-like structures and self-develop, closely mimicking embryo development. Ultimately, we aim to employ our embryo models as platforms to produce patient matched high-quality cells, paving the way for medical applications.
Contact us if you are enthusiastic about this topic and interested in our Research. We have PhD, Research Assistant, and postdoctoral positions available. We need your help to further our Research! You can also count on us to assist you develop your scientific skills.
Creating novel mouse and human model systems that can mimic embryo development in vitro
Our lab is interested in creating novel mouse and human model systems that can mimic embryo development in vitro by combining ideas from developmental biology research with reprogramming. We think that embryo models will be a great system to researching developmental biology and to generating relevant cell types for potential medical applications.
From embryo founder-like cells to Advanced Embryo Models
Image credit: Wei Guan
Generate cell types and tissues that are molecularly and functionally identical to their in vivo counterparts
By improving embryo models and making them closely resemble embryonic development, our goal is to create cell types and tissues that are molecularly and functionally identical to their in vivo counterparts. Our understanding is that such cell products/tissues will eventually possess the required quality to enable applications in medicine.
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