Publications by authors named "Leila Christie"
The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos.
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- Many mammals, including mice, can delay development between conception and birth by entering a dormant state during the blastocyst stage.
- Research shows that reducing the mTOR signaling pathway activity can induce this dormant state in human pluripotent stem cells and blastoids, leading to limited growth and development.
- This discovery suggests that humans also have the ability to enter dormancy around the blastocyst stage, which could have important implications for reproductive therapies.
During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development.
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- Development involves key interactions between the epiblast, trophectoderm, and hypoblast, which play crucial roles in forming the embryo, placenta, and yolk sac, respectively.
- Recent studies using human embryos and stem cell models have revealed how these signaling interactions occur after implantation, with specific dependencies on factors like NODAL and BMP.
- The research demonstrates both conserved and unique requirements for embryonic development in humans compared to mice, underscoring the importance of comparing different species to better understand human embryogenesis.
Article Synopsis
- * This study evaluated different methods for predicting gene regulatory networks (GRN) and found that using transcripts per million (TPM) for expression normalization yielded better predictions, with a focus on the MICA method based on mutual information.
- * MICA successfully identified complex interactions within the early human development GRN, including the interaction of transcription factors JUND and TFAP2C, demonstrating a valuable pipeline for future single-cell multi-omics studies.
Our understanding of the molecular events driving cell specification in early mammalian development relies mainly on mouse studies, and it remains unclear whether these mechanisms are conserved across mammals, including humans. We have shown that the establishment of cell polarity via aPKC is a conserved event in the initiation of the trophectoderm (TE) placental programme in mouse, cow and human embryos. However, the mechanisms transducing cell polarity into cell fate in cow and human embryos are unknown.
View Article and Find Full Text PDFCurrent knowledge of the transcriptional regulation of human pluripotency is incomplete, with lack of interspecies conservation observed. Single-cell transcriptomics analysis of human embryos previously enabled us to identify transcription factors, including the zinc-finger protein KLF17, that are enriched in the human epiblast and naïve human embryonic stem cells (hESCs). Here, we show that KLF17 is expressed coincident with the known pluripotency-associated factors NANOG and SOX2 across human blastocyst development.
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- Human embryo development involves significant shape changes after implantation, but the specific molecular processes are not fully understood in humans, unlike in mice.
- Researchers studied events in human embryos between implantation and gastrulation using single-cell analysis, highlighting that embryonic epiblast cells shift through different states and produce FGF signals for tissue growth.
- They identified a unique group of extra-embryonic hypoblast cells that could serve as an anterior signaling center, influencing the development of the embryo's front and back (anterior-posterior axis).
Current understandings of cell specification in early mammalian pre-implantation development are based mainly on mouse studies. The first lineage differentiation event occurs at the morula stage, with outer cells initiating a trophectoderm (TE) placental progenitor program. The inner cell mass arises from inner cells during subsequent developmental stages and comprises precursor cells of the embryo proper and yolk sac.
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- The research investigates the signalling pathways that regulate early human development by analyzing transcriptomics datasets, focusing on insulin and IGF1 receptors and their ligand.
- The study creates a specialized culture medium using IGF1 and Activin, enabling the maintenance of pluripotent stem cells without FGF signalling, while producing viable stem cell lines capable of genetic modification and differentiation.
- It also reveals active PI3K/AKT/mTOR signalling in early human embryos, suggesting that insights from human blastocysts can help optimize culture conditions that mimic embryonic environments more effectively.
There were errors published in Development 142, 3151-3165.In the issue published online on 22 September 2015, Fig. 3 was mislabelled: panels A, B, C and D should have been B, C, D and A, respectively.
View Article and Find Full Text PDFHere, we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression.
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