Lightnews — Scholar-powered news

Tianxiong (Bear) Yu

@tianxiong-bear-yu.bsky.social

78 followers 150 following 14 posts

Instructor in UMass Chan Medical School. Focus on using Computational Methods to study transposons in human and koala genomes.

Posts Media Videos Starter Packs

Pinned

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

As we age, our brains change at both the genomic and transcriptomic levels. 🧠✨
In our new Nature @nature.com paper, we map these changes at single-cell resolution in the human prefrontal cortex from infancy to centenarian.
Honored to lead the data analysis and be co-first author on this work!

Single-cell transcriptomic and genomic changes in the ageing human brain - Nature

Sequencing analyses of human prefrontal cortex from donors ranging in age from 0.4 to 104 years show that ageing correlates with an accumulation of somatic mutations in short housekeeping genes a...

www.nature.com

1 2

Reposted by Tianxiong (Bear) Yu

Prof Steven Lee @stevethechemist.bsky.social · 8d

Our work on visualising protein aggregates in human brain tissue in Parkinson's disease was published today in Nature Biomedical Engineering, well done to Becs, Bin and Christina for their hardwork!
www.cam.ac.uk/research/new...

Parkinson’s ‘trigger’ directly observed in human brain tissue for the first time

Scientists have, for the first time, directly visualised and quantified the protein clusters believed to trigger Parkinson’s, marking a major advance in the

www.cam.ac.uk

9 41

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

5/5. I’m deeply grateful to my amazing co-first author Ailsa Jeffries — it was a joy to work together on this project. Special thanks to my mentors Michael Lodato and Zhiping Weng for their guidance and support throughout this work.

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

4/5. Finally, a linear model showed that high basal expression and short gene length are linked to decreased expression with ageing.
Housekeeping genes are short and highly active. Our analysis suggests they are prone to damage, mutation, and disrupted expression and function during ageing.

a, Mixed-effects linear model identifying determinants of downregulation in excitatory neurons (model performance R2=0.54). Gene and exon length positively correlated with ageing-related fold change (FC) in expression. Length-normalized expression in excitatory neurons and frontal cortex expression (GTEx database) negatively correlated with ageing-related fold change. Significance of linear model correlations was determined by two-sided t-test. b, Density plots of the length of downregulated genes (solid lines) and all expressed genes (dashed lines) for each cell type. Mean lengths for downregulated genes are shown; asterisks denote significant differences from the mean neuronal downregulated length. c, Expression of topoisomerase complex genes across cell types. Asterisks denote significant differences in the percentage of cells expressing between neurons and non-neurons (two-sided Wilcoxon rank-sum test). d, Housekeeping genes (n=1,802) are significantly shorter than neuron-specific genes (n=288). e, Short (decile 1) housekeeping and neuron-specific genes showed differential expression in adult excitatory neurons CPKM, counts per kilobase per million. f,g, Fold change (elderly/adult) of housekeeping genes (f) and neuron-specific genes (g) by length decile in excitatory neurons.

1 1

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

3/5. Using scWGS, we identified somatic SNVs in neurons. Signature analysis revealed a predominant age-related mutation signature (A1; mainly C>T and T>C). Signature A1 mutations accumulate at ~12.1 per neuron per year and are likely driven by transcriptional activity.

a, De novo mutational signature analysis of sSNVs in human neurons revealed two signatures: A1 dominated by T>C mutations and A2 dominated by C>T mutations. b, Number of signature A1 sSNVs in each neuron plotted by age. Signature A1 strongly correlates with age (R2 = 0.88) with an extrapolated mutation rate of 12.1 SNVs per year. c, sSNV enrichment of signature A1 in coding regions plotted by neuron expression quantile (left) and genic versus intergenic regions (right). Signature A1 is enriched in the highest-expressed genes and genic regions (chi-squared test). d, Percentage of total sSNVs derived from the transcribed strand broken down by expression quantile. T>C and C>T strand bias increases with expression. e, Number of signature A2 sSNVs in each neuron plotted by age. Signature A2 correlates with age (R2 = 0.42) with an extrapolated mutation rate of 3 SNVs per year. f, sSNV enrichment of signature A2 in coding regions plotted by neuron expression quantile (left) and genic versus intergenic regions (right). Signature A2 is depleted in the highest-expressed genes and enriched in the lowest-expressed genes as well as intergenic regions.

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

2/5. We further found that housekeeping genes (involved in ribosomes, transport, and metabolism) show a common decrease in expression across both neurons and glia. Conversely, neuron-specific gene expression generally remains stable throughout life.

a, Number of downregulated (blue) and upregulated (red) genes for each cell type in elderly donors. DEGs, differentially expressed genes. b, Heat map of significantly downregulated differentially expressed genes in elderly donors. Genes not differentially expressed are in white. The leftmost genes are defined as common across cell types (down in one or more excitatory, one or more inhibitory and two or more non-neuronal cell types). c, GO terms of genes downregulated in ageing plotted as general categories. Housekeeping functions (shades of blue) are commonly downregulated. d, Housekeeping genes are significantly downregulated in elderly relative to adult brains in all neuron types. e, Mean gene effect score for all of the downregulated (blue) and upregulated (red) genes (in elderly versus adult donors) in the DepMap database. The downregulated genes for both neurons (left) and microglia (right) are more essential than the upregulated genes.

1 1

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

1/5. Using snRNA-seq, we found no differences in the overall ratios of neurons to glia or excitatory to inhibitory neurons. However, we identified subtypes of excitatory neurons and astrocytes unique to the infant PFC. These infant-specific cells are enriched for neurodevelopmental genes.

Clusters plotted by donor contribution as a percentage of total cells in the cluster. L2/3-2 and Ast-3 are composed nearly completely of nuclei from infant donors

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Sep 3

Single-cell transcriptomic and genomic changes in the ageing human brain - Nature

Sequencing analyses of human prefrontal cortex from donors ranging in age from 0.4 to 104 years show that ageing correlates with an accumulation of somatic mutations in short housekeeping genes a...

www.nature.com

1 2

Reposted by Tianxiong (Bear) Yu

Michael Haslam @twigtechnology.bsky.social · Aug 26

New study led by Joanna Baker shows bigger brains and relatively longer thumbs coevolved in primates. Humans have huge thumbs, but only what our brain size (esp. neocortex) would predict. It’s NOT driven by tool use.

A fantastic paper with a huge amount of work, and superb data presentation 🧪🏺👍🧠💀🐒🦧

Human dexterity and brains evolved hand in hand - Communications Biology

Thumbs and brains coevolved in primates. Across living and extinct species, longer thumbs predict bigger brains, highlighting the neural cost of dexterity.

www.nature.com

2 36 93

Reposted by Tianxiong (Bear) Yu

Julius Brennecke @juliusbrennecke.bsky.social · Jul 16

Pls. share widely

Calling all transposon fans & lovers of genetic innovation

MOBILE GENOME welcomes you in Heidelberg, Nov. 4–7 2025

→ Vibrant & friendly community
→ Cutting-edge talks from mechanisms to physiology
→ Plenty of surprises (TEs never stop innovating)

submit abstract by July 29

EMBL Events @events.embl.org · Jun 18

⏰ Abstract deadline for 'The mobile genome' is 29 July!

👉 https://s.embl.org/mge25-01-bl

Join us 4–7 Nov 2025 at EMBL Heidelberg (or online) to explore the impact of TEs across biology. 🧬🔍

⭐🧑🏼‍🔬 24 talks + 15 flash talks from posters – don't miss out!

#EMBOMobileGenome

1 48 61

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Jul 10

Finally got my personal academia website done. I am glad it looks well-organized for both laptop and phone.
Big shout to "Academia Pages" GitHub pages template.
tianxiongbb.github.io

About me

tianxiongbb.github.io

Reposted by Tianxiong (Bear) Yu

Selin Jessa @selinjessa.bsky.social · May 3

Delighted to share our latest work deciphering the landscape of chromatin accessibility and modeling the DNA sequence syntax rules underlying gene regulation during human fetal development! www.biorxiv.org/content/10.1... Read on for more: 🧵 1/16 #GeneReg 🧬🖥️

Dissecting regulatory syntax in human development with scalable multiomics and deep learning

Transcription factors (TFs) establish cell identity during development by binding regulatory DNA in a sequence-specific manner, often promoting local chromatin accessibility, and regulating gene expre...

www.biorxiv.org

2 59 130

Reposted by Tianxiong (Bear) Yu

Cell - a Cell Press journal @cp-cell.bsky.social · Apr 17

The new issue is out! 👉 cell.com/cell/current
⁠
In this issue of Cell, Yu et al. capture evolution of KoRV-A transcriptional silencing as the virus transitions from a pathogen to a stable endogenous retrovirus. The cover features an adult koala with a joey.

📷 Credit: Currumbin Wildlife Sanctuary

1 4 14

Reposted by Tianxiong (Bear) Yu

Jim Johnson 🇨🇦 @jimjohnsonsci.bsky.social · Apr 4

www.nature.com/naturecareer... UBC LSI Job!!

Assistant Professor (tenure track) – Chromatin, Epigenetics - Vancouver, British Columbia (CA) job with The University of British Columbia (UBC) | 12837841

Assistant Professor (tenure track) - Chromatin Regulation, Genetic Regulatory Mechanisms, Epigenetics, Epigenomics

www.nature.com

36 32

Reposted by Tianxiong (Bear) Yu

Nature @nature.com · Mar 29

🧪 A paralysed man can stand on his own after receiving an injection of neural stem cells to treat his spinal cord injury

https://go.nature.com/4jaZ3RB

Paralysed man stands again after receiving ‘reprogrammed’ stem cells

Nature - Another man also regained some movement, but two others experienced minimal improvement.

go.nature.com

8 50 270

Reposted by Tianxiong (Bear) Yu

Johan Jakobsson @jakobssonlab.bsky.social · Mar 29

New preprint from our lab! Why is not everyone working on Transposons?

Loss of H3K9me3 maintenance in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons

www.biorxiv.org/content/10.1...

Loss of H3K9me3 maintenance in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons

Heterochromatin is characterised by an inaccessibility to the transcriptional machinery and associated with the histone mark H3K9me3. Heterochromatin erosion is a hallmark of human ageing and H3K9me3 ...

www.biorxiv.org

2 24 73

Reposted by Tianxiong (Bear) Yu

Julius Brennecke @juliusbrennecke.bsky.social · Mar 29

We are seeking a new colleague to join us at the Vienna BioCenter, specifically at my beloved home institution, IMBA @imbavienna.bsky.social

we value collegiality and a passion for curiosity driven science. Being a great and fun human being also helps!

Institute of Molecular Biotechnology @imbavienna.bsky.social · Mar 28

IMBA is recruiting a Junior Group Leader! Are you interested in starting your own lab, pursuing curiosity-driven basic research in the life sciences? Apply now to our group leader position. The deadline is May 28. Link is below.

42 50

Reposted by Tianxiong (Bear) Yu

Dr. Tyler A. Elliott @transposableman.bsky.social · Mar 21

#TEsky The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition doi.org/10.7554/eLif...

The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition

DNA hypomethylation in human tumor cells results in the activation of the LINE-1-derived RNA-binding protein L1TD1 and its interactions with LINE-1 transposons.

doi.org

16 22

Reposted by Tianxiong (Bear) Yu

@LaBonneLaB @labonnelab.bsky.social · Mar 19

Super exciting and beautiful new work from the talented @mathithiru.bsky.social www.nature.com/articles/s41...

Repurposing of a gill gene regulatory program for outer-ear evolution - Nature

A study on the evolutionary origin of the mammalian outer ear finds that it shares genetic programs with the gills of fishes and amphibians, indicating that elements of an ancestral gill have been reu...

www.nature.com

13 42

Reposted by Tianxiong (Bear) Yu

Julius Brennecke @juliusbrennecke.bsky.social · Mar 17

In the ‘90s, Pelisson et al. found that gypsy retrotransposons in flies can go viral—literally—thanks to an envelope gene. Now, @mayavoichek.bsky.social uncovers a wild new path to retrotransposon infectivity. A fascinating story—see Maya's thread
www.biorxiv.org/content/10.1101/2025.03.14.642691v2

24 79

Reposted by Tianxiong (Bear) Yu

UMass Chan Medical School @umasschan.bsky.social · Mar 17

Working with a team at the University of Queensland, UMass Chan scientists have discovered that a population of koalas has evolved genomic immunity to a retrovirus: direc.to/mDfy

#koalas @lubanlab.bsky.social @tianxiong-bear-yu.bsky.social

William E. Theurkauf, PhD; Jeremy Luban, MD; Tianxiong Yu, PhD; and Zhiping Weng, PhD

3 9

Reposted by Tianxiong (Bear) Yu

Saez-Rodriguez Group @saezlab.bsky.social · Mar 14

📄 Update on our preprint about Gene Regulatory Net (GRN) benchmarking 📄
We have included the original and decoupled version of SCENIC+, added a new metric and two more databases. Dictys and SCENIC+ outperformed others, but still performed poorly in causal mechanistic tasks.
doi.org/10.1101/2024... 👇

Performance of multimodal GRN inference methods. SCENIC+ and Dictys outperform others.

2 18 50

Reposted by Tianxiong (Bear) Yu

Wayo Matsushima @wayomayo.bsky.social · Mar 10

New preprint of my postdoc work! We found a novel group of zinc-finger proteins that rapidly evolved in a lineage-specific manner to repress regulatory activities of transposon-derived sequences through anchoring nucleosomes. #TEsky

biorxiv.org/content/10.110…

4 10 33

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Mar 9

6/6. The two-phased response mirrors the innate and adaptive immunity: first recognize the pattern then the sequence of a new invader. Analyzing 400+ published koala DNA-seq data revealed the second phase response trigger – MAP4K4 KoRV-A provirus – is under selection and sweeping to fixation.

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Mar 9

5/6. The antisense piRNAs directs its binding partner PIWI to recruit DNA methylation machinery co-transcriptionally at KoRV-A proviruses genome wide, leading to a 10–fold decreasing of KoRV-A expression compared to koalas without the MAP4K4 provirus.

K94276 (green): koala with the MAP4K4 provirus.
K98224 (blue): koala without the MAP4K4 provirus

1 2

Tianxiong (Bear) Yu @tianxiong-bear-yu.bsky.social · Mar 9

4/6. We identified the second phase in koalas north of the River. It was triggered when the KoRV-A sequence was captured by a genic (i.e. MAP4K4) 3´UTR. Transcripts antisense to KoRV-A are made, as well as antisense piRNAs processed from these transcripts.

1 2