Summary
At the onset of mammalian life, the first lineage specification decision is made where embryonic cells opt to
become either part of the placenta or the future body. Proper regulation of this choice is crucial for subsequent
development. However, we don’t know how the transcription program and 3D genome architecture arise,
interconnect, and are controlled to determine the fate of each cell in a developing embryo. Recent studies,
including my work, suggest that in addition to canonical mRNA-coding genes, RNAs from the “dark” parts of
the genome (e.g., transposons, repeats, long-non-coding RNAs) play a significant role during these events, yet
how specific classes of RNA regulate gene expression and nuclear architecture post fertilization remains
elusive. The main aim of my proposal is to understand the interrelationship between 3D genome organization
and the transcriptome across early development and to identify novel factors that lead to the first cell-fate
decision and concomitant decrease in cell potency.
Recent technical advances, which I co-developed, enabled simultaneous measurement of 3D genome
organization and the transcriptome, and facilitated large-scale functional screens in early mammalian embryos.
Thus, I now propose to generate spatiotemporal maps of 3D DNA and RNA organization from early mouse
embryos at single-cell resolution (Obj.1) to build a complete picture of the relationships between nuclear
architecture and emerging cell-type specific transcriptome that drive early cell fate choices. I will combine
these data with large-scale in vivo perturbations targeting protein coding genes (Obj.2) and dark genome
RNAs (Obj.3) to identify key inducers/regulators of lineage specification and to determine molecular
mechanisms governing cell-state transitions. The proposed research will help us to control, correct, and
eventually employ early stages of embryonic development and their high cell potency in vitro in reproductive
medicine and stem cell research.
become either part of the placenta or the future body. Proper regulation of this choice is crucial for subsequent
development. However, we don’t know how the transcription program and 3D genome architecture arise,
interconnect, and are controlled to determine the fate of each cell in a developing embryo. Recent studies,
including my work, suggest that in addition to canonical mRNA-coding genes, RNAs from the “dark” parts of
the genome (e.g., transposons, repeats, long-non-coding RNAs) play a significant role during these events, yet
how specific classes of RNA regulate gene expression and nuclear architecture post fertilization remains
elusive. The main aim of my proposal is to understand the interrelationship between 3D genome organization
and the transcriptome across early development and to identify novel factors that lead to the first cell-fate
decision and concomitant decrease in cell potency.
Recent technical advances, which I co-developed, enabled simultaneous measurement of 3D genome
organization and the transcriptome, and facilitated large-scale functional screens in early mammalian embryos.
Thus, I now propose to generate spatiotemporal maps of 3D DNA and RNA organization from early mouse
embryos at single-cell resolution (Obj.1) to build a complete picture of the relationships between nuclear
architecture and emerging cell-type specific transcriptome that drive early cell fate choices. I will combine
these data with large-scale in vivo perturbations targeting protein coding genes (Obj.2) and dark genome
RNAs (Obj.3) to identify key inducers/regulators of lineage specification and to determine molecular
mechanisms governing cell-state transitions. The proposed research will help us to control, correct, and
eventually employ early stages of embryonic development and their high cell potency in vitro in reproductive
medicine and stem cell research.
Unfold all
/
Fold all
More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101077048 |
| Start date: | 01-06-2023 |
| End date: | 31-05-2028 |
| Total budget - Public funding: | 1 500 000,00 Euro - 1 500 000,00 Euro |
Cordis data
Original description
At the onset of mammalian life, the first lineage specification decision is made where embryonic cells opt tobecome either part of the placenta or the future body. Proper regulation of this choice is crucial for subsequent
development. However, we don’t know how the transcription program and 3D genome architecture arise,
interconnect, and are controlled to determine the fate of each cell in a developing embryo. Recent studies,
including my work, suggest that in addition to canonical mRNA-coding genes, RNAs from the “dark” parts of
the genome (e.g., transposons, repeats, long-non-coding RNAs) play a significant role during these events, yet
how specific classes of RNA regulate gene expression and nuclear architecture post fertilization remains
elusive. The main aim of my proposal is to understand the interrelationship between 3D genome organization
and the transcriptome across early development and to identify novel factors that lead to the first cell-fate
decision and concomitant decrease in cell potency.
Recent technical advances, which I co-developed, enabled simultaneous measurement of 3D genome
organization and the transcriptome, and facilitated large-scale functional screens in early mammalian embryos.
Thus, I now propose to generate spatiotemporal maps of 3D DNA and RNA organization from early mouse
embryos at single-cell resolution (Obj.1) to build a complete picture of the relationships between nuclear
architecture and emerging cell-type specific transcriptome that drive early cell fate choices. I will combine
these data with large-scale in vivo perturbations targeting protein coding genes (Obj.2) and dark genome
RNAs (Obj.3) to identify key inducers/regulators of lineage specification and to determine molecular
mechanisms governing cell-state transitions. The proposed research will help us to control, correct, and
eventually employ early stages of embryonic development and their high cell potency in vitro in reproductive
medicine and stem cell research.
Status
SIGNEDCall topic
ERC-2022-STGUpdate Date
31-07-2023
Images
No images available.
Geographical location(s)
