Taro Kitazawa
@kitazawa-taro.bsky.social
Group Leader at DANDRITE Nordic-EMBL/Aarhus Univ.
ERC Research, FensKavli Scholar.
Molecular basis of neuroplasticity.
New genomics technologies.
https://www.kitazawa-lab.com/home
ERC Research, FensKavli Scholar.
Molecular basis of neuroplasticity.
New genomics technologies.
https://www.kitazawa-lab.com/home
Reposted by Taro Kitazawa
In summary, we established whole-genome, multimodal single-cell history tracing, applicable to a wide range of experimental systems.
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
August 16, 2025 at 7:15 AM
In summary, we established whole-genome, multimodal single-cell history tracing, applicable to a wide range of experimental systems.
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
Thanks, Marek!
Indeed, your nanobody-Tn5 protocol is AMAZING!
We actually put some modifications, like sample-bcd implementation, as well as replacement of enzyme for 10x reaction, which may be interesting for you.
I look forward to discussing with you again!
Indeed, your nanobody-Tn5 protocol is AMAZING!
We actually put some modifications, like sample-bcd implementation, as well as replacement of enzyme for 10x reaction, which may be interesting for you.
I look forward to discussing with you again!
August 18, 2025 at 8:59 PM
Thanks, Marek!
Indeed, your nanobody-Tn5 protocol is AMAZING!
We actually put some modifications, like sample-bcd implementation, as well as replacement of enzyme for 10x reaction, which may be interesting for you.
I look forward to discussing with you again!
Indeed, your nanobody-Tn5 protocol is AMAZING!
We actually put some modifications, like sample-bcd implementation, as well as replacement of enzyme for 10x reaction, which may be interesting for you.
I look forward to discussing with you again!
Thank you so much!!
August 16, 2025 at 11:00 AM
Thank you so much!!
Thank you so much, Oliver!
August 16, 2025 at 7:25 AM
Thank you so much, Oliver!
This work was carried out by our super talented postdocs Yumiko K Kawamura and Valentina Khalil with generous supports of @dandrite.bsky.social, @erc.europa.eu, @lundbeckfonden.bsky.social, @novo-nordisk.bsky.social, JST, and Aarhus University.
August 16, 2025 at 7:15 AM
This work was carried out by our super talented postdocs Yumiko K Kawamura and Valentina Khalil with generous supports of @dandrite.bsky.social, @erc.europa.eu, @lundbeckfonden.bsky.social, @novo-nordisk.bsky.social, JST, and Aarhus University.
In summary, we established whole-genome, multimodal single-cell history tracing, applicable to a wide range of experimental systems.
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
August 16, 2025 at 7:15 AM
In summary, we established whole-genome, multimodal single-cell history tracing, applicable to a wide range of experimental systems.
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
Our lab is now applying HisTrac to study id specification and plasticity (e.g., memory) and we look forward to sharing exciting results soon!
We next explored the mechanisms underlying this hidden layer of developmental plasticity and found that identity jumps are associated with precocious activation of maturation programs, altered cell–cell interactions and downstream signaling, and resolution of enhancer bivalency.
August 16, 2025 at 7:15 AM
We next explored the mechanisms underlying this hidden layer of developmental plasticity and found that identity jumps are associated with precocious activation of maturation programs, altered cell–cell interactions and downstream signaling, and resolution of enhancer bivalency.
Such abrupt identity jumps were previously unobservable with current single-cell technologies, as trajectory inference relies on continuity between single-cell snapshots.
August 16, 2025 at 7:15 AM
Such abrupt identity jumps were previously unobservable with current single-cell technologies, as trajectory inference relies on continuity between single-cell snapshots.
Time for biology:
Using scHisTrac-seq to profile transcriptome, chromatin accessibility, and bivalency during neurodifferentiation, we analyzed over 90,000 single cells and uncovered drastic cell identity transitions—namely “identity jumps.
Using scHisTrac-seq to profile transcriptome, chromatin accessibility, and bivalency during neurodifferentiation, we analyzed over 90,000 single cells and uncovered drastic cell identity transitions—namely “identity jumps.
August 16, 2025 at 7:15 AM
Time for biology:
Using scHisTrac-seq to profile transcriptome, chromatin accessibility, and bivalency during neurodifferentiation, we analyzed over 90,000 single cells and uncovered drastic cell identity transitions—namely “identity jumps.
Using scHisTrac-seq to profile transcriptome, chromatin accessibility, and bivalency during neurodifferentiation, we analyzed over 90,000 single cells and uncovered drastic cell identity transitions—namely “identity jumps.
So far, so good—perhaps too good.
For the final form, we developed scHisTrac-seq, enabling simultaneous profiling of past and present multiomic states from the same single cells via a nanobody-mediated dual scCUT&Tag protocol (past = m6A, present = H3K27ac, transcription marker).
For the final form, we developed scHisTrac-seq, enabling simultaneous profiling of past and present multiomic states from the same single cells via a nanobody-mediated dual scCUT&Tag protocol (past = m6A, present = H3K27ac, transcription marker).
August 16, 2025 at 7:15 AM
So far, so good—perhaps too good.
For the final form, we developed scHisTrac-seq, enabling simultaneous profiling of past and present multiomic states from the same single cells via a nanobody-mediated dual scCUT&Tag protocol (past = m6A, present = H3K27ac, transcription marker).
For the final form, we developed scHisTrac-seq, enabling simultaneous profiling of past and present multiomic states from the same single cells via a nanobody-mediated dual scCUT&Tag protocol (past = m6A, present = H3K27ac, transcription marker).
We also achieved sample multiplexing within the 10x Genomics microfluidics, dramatically reducing single-cell library preparation costs to just $0.04 per cell.
August 16, 2025 at 7:15 AM
We also achieved sample multiplexing within the 10x Genomics microfluidics, dramatically reducing single-cell library preparation costs to just $0.04 per cell.
To fully leverage history tracing, we developed a single-cell m6A detection method on the 10x Genomics platform. By targeting Tn5 transposase via the m6A-tracer, we captured in vivo sc profiles with 5–10K unique reads—among the highest quality achieved for 10x-based assays.
August 16, 2025 at 7:15 AM
To fully leverage history tracing, we developed a single-cell m6A detection method on the 10x Genomics platform. By targeting Tn5 transposase via the m6A-tracer, we captured in vivo sc profiles with 5–10K unique reads—among the highest quality achieved for 10x-based assays.
We next validated HisTrac-seq in vivo, pulse-labeling the neonatal brain and harvesting in adulthood (8 weeks).
This captured neonatal epigenome and transcriptome in the adult brain, demonstrating that HisTrac-seq remains effective for at least two months in vivo!
This captured neonatal epigenome and transcriptome in the adult brain, demonstrating that HisTrac-seq remains effective for at least two months in vivo!
August 16, 2025 at 7:15 AM
We next validated HisTrac-seq in vivo, pulse-labeling the neonatal brain and harvesting in adulthood (8 weeks).
This captured neonatal epigenome and transcriptome in the adult brain, demonstrating that HisTrac-seq remains effective for at least two months in vivo!
This captured neonatal epigenome and transcriptome in the adult brain, demonstrating that HisTrac-seq remains effective for at least two months in vivo!
We first demonstrated bulk HisTrac-seq in vitro, showing that transient Dam–POI activation in immature neurons beautifully reproduced their profiles after maturation!
In addition, we extended the validation to the mesodermal cardiomyocyte lineage.
In addition, we extended the validation to the mesodermal cardiomyocyte lineage.
August 16, 2025 at 7:15 AM
We first demonstrated bulk HisTrac-seq in vitro, showing that transient Dam–POI activation in immature neurons beautifully reproduced their profiles after maturation!
In addition, we extended the validation to the mesodermal cardiomyocyte lineage.
In addition, we extended the validation to the mesodermal cardiomyocyte lineage.
By transiently activating Dam fused to POIs (proteins of interest), HisTrac-seq can record whole-genome multiomic profiles, including transcriptome, open chromatin, LAD-heterochromatin, Trithorax, Polycomb, and even bivalency.
August 16, 2025 at 7:15 AM
By transiently activating Dam fused to POIs (proteins of interest), HisTrac-seq can record whole-genome multiomic profiles, including transcriptome, open chromatin, LAD-heterochromatin, Trithorax, Polycomb, and even bivalency.
We used Dam (DNA adenine methyltransferase) to label DNA with m6A, a mark absent from our genome.
Because previously shown that m6A can persist for several hours until the next DNA replication, we expected it to serve as a long-term ”bookmark” in neurons, potentially for months.
Because previously shown that m6A can persist for several hours until the next DNA replication, we expected it to serve as a long-term ”bookmark” in neurons, potentially for months.
August 16, 2025 at 7:15 AM
We used Dam (DNA adenine methyltransferase) to label DNA with m6A, a mark absent from our genome.
Because previously shown that m6A can persist for several hours until the next DNA replication, we expected it to serve as a long-term ”bookmark” in neurons, potentially for months.
Because previously shown that m6A can persist for several hours until the next DNA replication, we expected it to serve as a long-term ”bookmark” in neurons, potentially for months.
While single-cell sequencing such as scRNA-seq are powerful, they inherently capture only static snapshots, and trajectory inference can only approximate dynamic processes. This has created a long-standing need for sc observations across multiple time points—history tracing.
August 16, 2025 at 7:15 AM
While single-cell sequencing such as scRNA-seq are powerful, they inherently capture only static snapshots, and trajectory inference can only approximate dynamic processes. This has created a long-standing need for sc observations across multiple time points—history tracing.
This approach revealed previously unseen, drastic cell identity transitions, namely “identity jumps” in the Waddington landscape, during neurodifferentiation.
Following threads will elaborate on HisTrac-seq and and our findings.
Following threads will elaborate on HisTrac-seq and and our findings.
August 16, 2025 at 7:15 AM
This approach revealed previously unseen, drastic cell identity transitions, namely “identity jumps” in the Waddington landscape, during neurodifferentiation.
Following threads will elaborate on HisTrac-seq and and our findings.
Following threads will elaborate on HisTrac-seq and and our findings.