I see the problem. In a sense, your question is a little ahead of the available datasets, but of course you need the data now. I imagine many groups are still limited by the cost and scale required for this kind of study. Nevertheless, I’ll keep it in mind and let you know if I come across something that looks suitable.
Ratz et al., Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics, Nature Neuroscience, 2022 and Mold et al., Clonally heritable gene expression imparts a layer of diversity within cell types, Cell Systems, 2024
Perhaps they don't fully meet your criteria, but they are very much in this space and might also refer to other papers or datasets that do. Michael Ratz is the person I was thinking of when I read what you need, so hopefully his publications could help you further even if these particular datasets are not completely suitable.
Thank you very much, Maria, this is a very valuable answer. After reviewing both papers, I would say that Ratz et al. 2022 has a very strong lineage tracing component, but the cortex/striatum/hippocampus represent different locations and developmental fates, not experimental perturbation branches created by the separation of a common population. Therefore, it is unlikely to be used as the main ME dataset, although it could be an excellent auxiliary or methodological dataset.
Mold et al. 2024 is a little bit closer to my hypothesis, as they examine the question of whether long-term, clonally heritable expression differences exist within the same cell type. They essentially performed a miniature precursor to my experiment. They showed that a clonal signature can survive independent reactivation and differentiation in separate environments. My project, however, goes a significant step further:
and an additional requirement: demonstrate that the effect must be relational and above simple average expression/state similarity.
Mold, on the other hand, only demonstrates that "a clone can carry a persistent transcriptional signature." It's not enough.
There is a fundamental problem with available datasets, because many lineage-tracing studies contain too few independent clones across genuinely different conditions, and statistical modelling or simulation cannot substitute for the missing biological replication required for this test.
I see the problem. In a sense, your question is a little ahead of the available datasets, but of course you need the data now. I imagine many groups are still limited by the cost and scale required for this kind of study. Nevertheless, I’ll keep it in mind and let you know if I come across something that looks suitable.
Such research certainly exists, but it's not yet publicly available. It's probably related to a potential new source of drugs. Well, patents.
Unfortunately, cross-sectional studies are on the back burner, if they're funded at all.
But thank you very much for keeping an eye on this.🫢
Two papers that might be worth checking are:
Ratz et al., Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics, Nature Neuroscience, 2022 and Mold et al., Clonally heritable gene expression imparts a layer of diversity within cell types, Cell Systems, 2024
Perhaps they don't fully meet your criteria, but they are very much in this space and might also refer to other papers or datasets that do. Michael Ratz is the person I was thinking of when I read what you need, so hopefully his publications could help you further even if these particular datasets are not completely suitable.
Thank you very much, Maria, this is a very valuable answer. After reviewing both papers, I would say that Ratz et al. 2022 has a very strong lineage tracing component, but the cortex/striatum/hippocampus represent different locations and developmental fates, not experimental perturbation branches created by the separation of a common population. Therefore, it is unlikely to be used as the main ME dataset, although it could be an excellent auxiliary or methodological dataset.
Mold et al. 2024 is a little bit closer to my hypothesis, as they examine the question of whether long-term, clonally heritable expression differences exist within the same cell type. They essentially performed a miniature precursor to my experiment. They showed that a clonal signature can survive independent reactivation and differentiation in separate environments. My project, however, goes a significant step further:
4 clones, replicate environments ⟶ ≥ 20 clones, ≥ 3 genuinely different perturbations
and an additional requirement: demonstrate that the effect must be relational and above simple average expression/state similarity.
Mold, on the other hand, only demonstrates that "a clone can carry a persistent transcriptional signature." It's not enough.
There is a fundamental problem with available datasets, because many lineage-tracing studies contain too few independent clones across genuinely different conditions, and statistical modelling or simulation cannot substitute for the missing biological replication required for this test.