Lineage tracing on transcriptional landscapes links state to fate during differentiation
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ABSTRACT:
PROVIDER: PRJNA591003 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we used expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate determination in hematopoiesis. We identified states of primed fate potential and located them on a continuous transcriptional landscape. We identified two routes of monocyte differentiation that leave an imprint on mature cells. Analysis of sister cells also revealed cells to have intrinsic fate biases not detectable by single-cell RNA sequencing. Finally, we benchmarked computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms and that cells progress steadily through pseudotime with precise and consistent dynamics.
| S-EPMC7608074 | biostudies-literature
Project description:A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we use expressed DNA barcodes to clonally trace transcriptomes over time, applied to study fate determination in hematopoiesis. We identify states of primed fate potential, and locate them on a continuous transcriptional landscape. We identify two routes of monocyte differentiation that leave an imprint on mature cells. Clonal analysis also reveals fate biases into multiple lineages that depend on stable cellular properties hidden from single-cell RNA sequencing. Finally, we benchmark computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms, and that cells progress steadily through pseudotime with precise and consistent dynamics.
2019-11-22 | GSE140802 | GEO
Project description:Vegfc lineage tracing identifies progenitor cells that change cell fate after musculoskeletal injury
| PRJNA1075123 | ENA
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223495 | GEO
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223494 | GEO
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223492 | GEO
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223491 | GEO
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223490 | GEO
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223489 | GEO
Project description:Cell plasticity is a core biological process underlying a myriad of molecular and cellular events taking place throughout organismal development and evolution. It has been postulated that cellular systems thrive to balance the organization of meta-stable states underlying this phenomenon, thus maintaining a degree of populational homeostasis compatible with an ever-changing environment and, thus, life. Notably, albeit circumstantial evidence has been gathered in favour of the latter conceptual framework, a direct observation of meta-state dynamics and the biological consequences of such a process in generating non-genetic clonal diversity and divergent phenotypic output remains largely unexplored. To fill this void, we developed a lineage-tracing technology termed Barcode-decay Lineage Tracing-Seq. BdLT-Seq is based on episome-encoded molecular identifiers that, supported by the dynamic decay of the tracing information upon cell division, ascribe directionality to a cell lineage tree in a time-resolved manner whilst directly coupling non-genetic molecular features to phenotypes in comparable genomic landscapes. Herein we show that cell transcriptome states are both inherited and dynamically reshaped following constrained rules encoded within the cell lineage, leading to intra-clonal non-genetic diversity in basal growth conditions and while adjusting populational phenotypic output upon oncogene activation and throughout the process of reversible resistance to therapeutic cues.
2023-02-11 | GSE223488 | GEO