Daniel Dan Liu
@daniel-liu.bsky.social
MD-PhD student @ Stanford Medicine with Irv Weissman, interested in human brain development, neural stem cells, and painting
Princeton '18
Princeton '18
The thing is, Cajal-Retzius cells mostly disappear by birth. This may be why the role of MIR137 has been so elusive: it's expressed transiently and specifically during development to help set up the layers of the cerebral cortex, but perhaps has less of a role after birth. 9/
August 15, 2025 at 11:02 PM
The thing is, Cajal-Retzius cells mostly disappear by birth. This may be why the role of MIR137 has been so elusive: it's expressed transiently and specifically during development to help set up the layers of the cerebral cortex, but perhaps has less of a role after birth. 9/
Cajal-Retzius cells are a super interesting class of neurons. They are among the earliest-born in the cortex, and occupy the outermost layer I. They guide subsequent neuron migration from the ventricular zone up into the cortical plate by secreting Reelin. 8/
August 15, 2025 at 11:02 PM
Cajal-Retzius cells are a super interesting class of neurons. They are among the earliest-born in the cortex, and occupy the outermost layer I. They guide subsequent neuron migration from the ventricular zone up into the cortical plate by secreting Reelin. 8/
And that schizophrenia risk gene, MIR137? We found it to be very specifically expressed in a special type of neurons called Cajal-Retzius cells. And it seems functional too—cells expressing MIR137 also had lower expression of MIR137 target genes. 7/
August 15, 2025 at 11:02 PM
And that schizophrenia risk gene, MIR137? We found it to be very specifically expressed in a special type of neurons called Cajal-Retzius cells. And it seems functional too—cells expressing MIR137 also had lower expression of MIR137 target genes. 7/
Many non-polyadenylated RNAs showed dynamic expression changes across excitatory and inhibitory neuron maturation, suggesting they may play a role in development. 6/
August 15, 2025 at 11:02 PM
Many non-polyadenylated RNAs showed dynamic expression changes across excitatory and inhibitory neuron maturation, suggesting they may play a role in development. 6/
...and got excellent recovery of all RNA classes, including non-polyadenylated ones, many of which showed cell-type specificity. 5/
August 15, 2025 at 11:02 PM
...and got excellent recovery of all RNA classes, including non-polyadenylated ones, many of which showed cell-type specificity. 5/
We applied this technology to the human brain across developmental timepoints and anatomical regions... 4/
August 15, 2025 at 11:02 PM
We applied this technology to the human brain across developmental timepoints and anatomical regions... 4/
Alina developed a new sequencing pipeline, called TotalX, which polyadenylates all transcripts prior to reverse transcription, allowing capture of all RNA classes. This pipeline is fully compatible with standard droplet-based
@10xgenomics.bsky.social 3' chemistry. 3/
@10xgenomics.bsky.social 3' chemistry. 3/
August 15, 2025 at 11:02 PM
Alina developed a new sequencing pipeline, called TotalX, which polyadenylates all transcripts prior to reverse transcription, allowing capture of all RNA classes. This pipeline is fully compatible with standard droplet-based
@10xgenomics.bsky.social 3' chemistry. 3/
@10xgenomics.bsky.social 3' chemistry. 3/
There are now several whole-brain atlases out there, but since most of them use polyA-based RNA capture, many classes of non-polyadenylated RNA get left out (miRNA, snRNA, snoRNA, tRNA, histone RNA, many viral RNAs, to name a few). 2/
August 15, 2025 at 11:02 PM
There are now several whole-brain atlases out there, but since most of them use polyA-based RNA capture, many classes of non-polyadenylated RNA get left out (miRNA, snRNA, snoRNA, tRNA, histone RNA, many viral RNAs, to name a few). 2/
Schizophrenia is highly heritable, and one of its strongest GWAS hits is actually a microRNA called MIR137. But where and when MIR137 is expressed has been a bit of a mystery, until now. A thread on a new preprint led by Alina Isakova and @stephenquake.bsky.social 1/
August 15, 2025 at 11:02 PM
Schizophrenia is highly heritable, and one of its strongest GWAS hits is actually a microRNA called MIR137. But where and when MIR137 is expressed has been a bit of a mystery, until now. A thread on a new preprint led by Alina Isakova and @stephenquake.bsky.social 1/
Primary human NSPCs thus make a great system for modeling gliomas, allowing for modular introduction of genetic manipulations into isogenic cell types at defined developmental stages. Being human cell lines, they also recapitulate human-specific cell types not found in mice. 10/
August 4, 2025 at 3:47 AM
Primary human NSPCs thus make a great system for modeling gliomas, allowing for modular introduction of genetic manipulations into isogenic cell types at defined developmental stages. Being human cell lines, they also recapitulate human-specific cell types not found in mice. 10/
To see if our results match up with real patient data, we reanalyzed some published GBM scRNA-seq datasets. Higher EGFR expression in the tumor indeed correlated with more GPC-like tumor cells. This suggests EGFR is not just a marker, but also a driver of the GPC-like state. 9/
August 4, 2025 at 3:47 AM
To see if our results match up with real patient data, we reanalyzed some published GBM scRNA-seq datasets. Higher EGFR expression in the tumor indeed correlated with more GPC-like tumor cells. This suggests EGFR is not just a marker, but also a driver of the GPC-like state. 9/
The mutation-of-origin had some even more dramatic effects, with CDK4 overexpression resulting in largely neuron-like tumor cells, and EGFR interestingly expanding the GPC-like tumor cells. 8/
August 4, 2025 at 3:47 AM
The mutation-of-origin had some even more dramatic effects, with CDK4 overexpression resulting in largely neuron-like tumor cells, and EGFR interestingly expanding the GPC-like tumor cells. 8/
The cell-of-origin had some interesting effects on the resulting tumor. NSC-derived tumors had the greatest cellular heterogeneity, while OPC-derived tumors harbored more differentiated oligodendrocyte-like cells. 7/
August 4, 2025 at 3:47 AM
The cell-of-origin had some interesting effects on the resulting tumor. NSC-derived tumors had the greatest cellular heterogeneity, while OPC-derived tumors harbored more differentiated oligodendrocyte-like cells. 7/
Our lines engrafted robustly, growing and migrating aggressively. We only transplanted the cells on one side of the brain, but here you can see them invading cross-hemisphere. 6/
August 4, 2025 at 3:47 AM
Our lines engrafted robustly, growing and migrating aggressively. We only transplanted the cells on one side of the brain, but here you can see them invading cross-hemisphere. 6/
So we asked: can we use these primary human NSPCs to model how cell-of-origin and mutation-of-origin drive different glioma subtypes?
Using isogenic NSC, GPC, and OPC neurosphere lines, we created glioma-like lines by introducing defined combinations of oncogenic driver genes. 5/
Using isogenic NSC, GPC, and OPC neurosphere lines, we created glioma-like lines by introducing defined combinations of oncogenic driver genes. 5/
August 4, 2025 at 3:47 AM
So we asked: can we use these primary human NSPCs to model how cell-of-origin and mutation-of-origin drive different glioma subtypes?
Using isogenic NSC, GPC, and OPC neurosphere lines, we created glioma-like lines by introducing defined combinations of oncogenic driver genes. 5/
Using isogenic NSC, GPC, and OPC neurosphere lines, we created glioma-like lines by introducing defined combinations of oncogenic driver genes. 5/
Even more interesting is that different glioma subtypes seem to embody different stem cell hierarchies: low-grade oligodendrogliomas have a lot of mature oligodendrocyte-like cells, while diffuse midline gliomas mostly contain OPC-like cells(Figure from Suvà& Tirosh, 2020). 3/
August 4, 2025 at 3:47 AM
Even more interesting is that different glioma subtypes seem to embody different stem cell hierarchies: low-grade oligodendrogliomas have a lot of mature oligodendrocyte-like cells, while diffuse midline gliomas mostly contain OPC-like cells(Figure from Suvà& Tirosh, 2020). 3/
Brain tumors known as gliomas are notoriously hard to treat, in part due to how heterogeneous the cancer cells are. In fact, glioma cells seem to mirror a corrupted neural stem cell hierarchy found in normal development. (Figure credit Neftel et al., 2019). 2/
August 4, 2025 at 3:47 AM
Brain tumors known as gliomas are notoriously hard to treat, in part due to how heterogeneous the cancer cells are. In fact, glioma cells seem to mirror a corrupted neural stem cell hierarchy found in normal development. (Figure credit Neftel et al., 2019). 2/
Cortical Development 2022 was the first conference I ever attended, and so it was particularly special to return to Sicily for @corticodevelopment.bsky.social 2025 as a speaker. Featuring a sneak peak on some exciting new findings on neural stem cells in the postnatal human brain (stay tuned!)
May 31, 2025 at 10:18 PM
Cortical Development 2022 was the first conference I ever attended, and so it was particularly special to return to Sicily for @corticodevelopment.bsky.social 2025 as a speaker. Featuring a sneak peak on some exciting new findings on neural stem cells in the postnatal human brain (stay tuned!)
Weissman Lab representing at the @isscr.org Athens International Symposium on Neural Stem Cells! Glad to share our work on purifying neural stem/progenitor cells from the human brain, and a preview of our work using those cells to model glioma heterogeneity.
April 7, 2025 at 8:22 PM
Weissman Lab representing at the @isscr.org Athens International Symposium on Neural Stem Cells! Glad to share our work on purifying neural stem/progenitor cells from the human brain, and a preview of our work using those cells to model glioma heterogeneity.
And here’s our final purification scheme! My hope is that this study provides a framework for studying the cellular basis of human brain development, including cell-autonomous functions and interactions between cell types. 14/
November 18, 2024 at 1:25 AM
And here’s our final purification scheme! My hope is that this study provides a framework for studying the cellular basis of human brain development, including cell-autonomous functions and interactions between cell types. 14/
These GPCs mostly lived in the outer subventricular zone, a layer of the cortex that is greatly expanded in primates. These cells may thus play an evolutionary role in the dramatic white matter expansion characteristic of human brains. 13/
November 18, 2024 at 1:25 AM
These GPCs mostly lived in the outer subventricular zone, a layer of the cortex that is greatly expanded in primates. These cells may thus play an evolutionary role in the dramatic white matter expansion characteristic of human brains. 13/
Because we had the index sort data, we could immediately figure out how to purify these cells. Through clonal differentiation and transplant assays, we found these cells made oligodendrocytes and astrocytes, but NOT neurons. We thus named it the glial progenitor cell (GPC). 12/
November 18, 2024 at 1:25 AM
Because we had the index sort data, we could immediately figure out how to purify these cells. Through clonal differentiation and transplant assays, we found these cells made oligodendrocytes and astrocytes, but NOT neurons. We thus named it the glial progenitor cell (GPC). 12/
And that’s that! Or so we thought, if not for this mysterious cluster in our scRNA-seq dataset. It expressed both astrocyte and oligodendrocyte markers. I thought it was an artefact, but we indeed found such cells in the human cortex with immunostaining. 11/
November 18, 2024 at 1:25 AM
And that’s that! Or so we thought, if not for this mysterious cluster in our scRNA-seq dataset. It expressed both astrocyte and oligodendrocyte markers. I thought it was an artefact, but we indeed found such cells in the human cortex with immunostaining. 11/
And then the neurons, which were CD24+THY1–. We can sort out early/late excitatory neurons as well as inhibitory neuron precursors, which uniformly give rise to neurons in vitro. 10/
November 18, 2024 at 1:25 AM
And then the neurons, which were CD24+THY1–. We can sort out early/late excitatory neurons as well as inhibitory neuron precursors, which uniformly give rise to neurons in vitro. 10/