Qi Chen

Perhaps our boldest hypothesis… we propose a model for RNA Structural Memory propagation in @natcellbio.nature.com where RNA conformation is reshaped by stress, locked by RBPs, copied prion-like in condensates & passed across generations—all without altering DNA rdcu.be/eBwPJ

@aaronquinlan.bsky.social

12 Sept

Hearty congratulations to Xudong on receiving an NIH K99 — one of our wishes during our lab anniversary trip has come true. Wishing you a golden future ahead!

Qi Chen@qichen-lab.bsky.social

A road trip to Monument Valley and the wonders of the west, as an anniversary of lab’s 10th year operation…look forward to the journey ahead…

Qi Chen reposted

Aaron Quinlan (he/him)

28 Aug

I am delighted to announce that The Department of Human Genetics at the University of Utah is continuing a multi-year recruiting initiative for multiple tenure-track faculty positions at the rank of Assistant Professor. Please share and consider applying! utah.peopleadmin.com/postings/208...

Qi Chen reposted

link.springer.comqMAP decodes RNA fragmentation dynamics in development and disease - Molecular Systems BiologyNoncanonical small RNAs, such as tRNA-derived (tsRNAs) and rRNA-derived (rsRNAs) fragments, are more abundant than microRNAs and arise from selective cleavage events rather than random degradation. Wh...

20 July

A tRNA/rRNA can be cleaved into different small RNAs with distinct functions depending on the cut site, yet abundance-based small RNA analysis is blind to it. Tong Zhou & us built a tool to read that hidden layer. Meet qMAP & the 'RNA fragmentome' @molsystbiol.org link.springer.com/article/10.1...

26 July

Adding to the intriguing story of Vault structures & their component Vault RNAs, we highlighted that Vault RNA-derived small RNAs (vtsRNAs) also bear biological functions: nature.com/articles/s41... It's Fascinating to see how nature always repurposes molecules for new functions! ♾

Science Magazine@science.org

Leonard Rome’s lab discovered an odd, abundant component of cells in the 1980s—and he’s still trying to figure out what it does. Learn more: https://scim.ag/4whygtn #ScienceMagArchives

go.nature.comDecoding the origins of cellular self-organization for engineered biology - Nature BiotechnologyThis Perspective positions cellular self-organization as a foundational principle for the origin of multicellular life and discusses how decoding this concept with stem cell-based models will advance ...

20 July

Qi Chen reposted

Nature Biotechnology

@natbiotech.nature.com

15 July

This Perspective positions cellular self-organization as a foundational principle for the origin of multicellular life and discusses how decoding this concept with stem cell-based models will advance biological engineering go.nature.com/4e1m3Br rdcu.be/ftZeL

2 June

After years of crystallization, in @natbiotech.nature.com, @zernickagoetz.bsky.social and I discuss the evolutionary origins of multicellularity & how physical constraints inevitably drive cellular self-organization. Harnessing these rules may help us better understand & engineer life rdcu.be/flTKa

Qi Chen reposted

Nature Biotechnology

@natbiotech.nature.com

1 June

Decoding the origins of cellular self-organization for engineered biology - @qichen-lab.bsky.social @zernickagoetz.bsky.social go.nature.com/4e1m3Br

Qi Chen reposted

Perhaps the most puzzling part: We see a paradox: the rsRNA length shift is progressive⏳yet the global RNA profile shows an "Aging Cliff"📉. Cliff or Progression? Maybe the gradual shift is the forerunner—accumulating silently until it triggers the cliff. bsky.app/profile/qich...

Qi Chen@qichen-lab.bsky.social

1/5 It took us some time to connect the dots...now in @embojournal.org we use PANDORA-seq to start decoding the 'sperm RNA code of aging' We find a conserved rsRNA length shift that reflects aging in both mouse & human sperm, and an 'aging cliff' at mid-life🧵 link.springer.com/article/10.1...

Qi Chen reposted

Science X / Phys.org

@sciencex.bsky.social

phys.orgScientists discover a hidden RNA 'aging clock' in human spermIncreasing paternal age has been linked to elevated health risks for the next generation, including higher risks of obesity and stillbirth.

A molecular "aging clock" has been identified in human sperm RNA, showing progressive changes with age that may influence offspring health and metabolism. doi.org/hbkmvf

Qi Chen reposted

Julie Kiefer

@julieckiefer.bsky.social

21 Jan

Fascinating research! Qi Chen and colleagues have identified a potential "aging cliff" in sperm RNA (rsRNA) that is associated with the increased health risks for the next generation that accompany advancing paternal age. Read on uofuhealth.utah.edu/newsroom/new...

uofuhealth.utah.eduScientists Discover a Hidden RNA “Aging Clock” in Human SpermThe molecular contents of sperm go through similar shifts over time in both mice and humans, which may lead to a rapid, dramatic shift at mid-life.

Qi Chen@qichen-lab.bsky.social

Qi Chen reposted

The EMBO Journal

@embojournal.org

link.springer.comConserved shifts in sperm small non-coding RNA profiles during mouse and human aging - The EMBO JournalSperm aging impacts male fertility and offspring health, highlighting the need for reliable aging biomarkers to guide reproductive decisions. However, the molecular determinants of sperm fitness durin...

What underlies the impact of sperm aging on fertility and offspring health? small ncRNA profiling by Kenneth Aston, Tong Zhou, @qichen-lab.bsky.social and colleagues reveals a drastic shift in RNA complements able to affect recipient cell metabolism link.springer.com/article/10.1...

Qi Chen@qichen-lab.bsky.social

4/5 Crucially, beyond mouse data, we validated the sperm-head-specific rsRNA length shift signal in two independent human cohorts (longitudinal & cross-sectional). This suggests an evolutionarily conserved feature, which may stem from shared (enzymatic) mechanisms during aging.

5/5 Connecting mouse and human sperm data to uncover this conserved rsRNA length shift has been a privilege. Made possible by unique resources at @uuhsresearch.bsky.social Huge thanks to the trainees & collaborators who made this happen! @jianchengyu.bsky.social @cai000chen.bsky.social

2/5 The first revelation: In mice, PANDORA-seq uncovers a sharp "Aging Cliff"📉in sperm RNA profiles at mid-life—a non-linear shift distinct from chronological age. Crucially, this cliff signal (genomic & mitochondrial tsRNAs/rsRNAs) is invisible to traditional small RNA-seq.

3/5 Perhaps the most surprising discovery: we see an age-dependent "Length Shift" in rsRNAs, exclusively found in sperm heads. Specifically, longer fragments accumulate while shorter ones decrease with age—a sign of altered RNA cleavage/processing efficiency (e.g., enzymatic).

25 Dec 2025

A road trip to Monument Valley and the wonders of the west, as an anniversary of lab’s 10th year operation…look forward to the journey ahead…

quantamagazine.orgHow Dad’s Fitness May Be Packaged and Passed Down in Sperm RNA | Quanta MagazineResearch into how a father’s choices, including diet, exercise, stress and nicotine use, may transfer traits to his children epigenetically has become impossible to ignore.

23 Dec 2025

Glad to see this thoughtful piece in @quantamagazine.bsky.social on paternal epigenetic inheritance and the emerging 'Sperm RNA Code', featuring many active colleagues in the field. It’s a reminder that our actions may echo in the next generation(s) & there are immense unknowns to explore...

Quanta Magazine@quantamagazine.org

In a recent study, the fitness of a father mouse at the time of conception was found to have metabolic and mitochondrial benefits for his offspring. Similar signatures were found in the sperm of well-exercised human men. @ivanamato.bsky.social reports: www.quantamagazine.org/how-dads-fit...

Qi Chen reposted

Bruno Di Stefano

@distefanolab.bsky.social

28 Oct 2025

1/ Excited to share our new study with @brumbaugh-lab.bsky.social, out in @natbiotech.nature.com! P-bodies selectively sequester RNAs encoding cell fate regulators, often from the preceding developmental stage. Releasing these RNAs can drive changes in cell identity. 🧵 www.nature.com/articles/s41...

nature.comSelective RNA sequestration in biomolecular condensates directs cell fate transitions - Nature BiotechnologyStem cell differentiation is controlled by manipulating RNA condensates.

academic.oup.comFUSION: a family-level integration approach for robust differential analysis of small non-coding RNAsAbstractMotivation. Beyond well-studied microRNAs, noncanonical small non-coding RNAs (sncRNAs) derived from longer parental templates such as tRNAs, rRNAs

18 Sept 2025

After developing PANDORA-seq to reveal hidden small RNAs (e.g., tsRNA, rsRNA) and SPORTS to annotate them, we now expand our toolchain with Tong Zhou lab: introducing FUSION, a tool that robustly interprets small RNA changes even in small or 1-on-1 datasets. academic.oup.com/bioinformati...

Beyond inheritance, the model may also apply to cancer & neurodegeneration, where abnormal RNA structures could shape pathological cell states. Perhaps misfolded RNAs — not just amyloid proteins — are the central structural entity driving disease.

Proud to work with a brave team @cai000chen.bsky.social‬ @jianchengyu.bsky.social‬ Xudong Zhang & Tong Zhou—thinking fearlessly to bring this piece together. In a time of uncertainty, may this idea be a seed for spring… We’ll see what evidence we and the community can bring, to confirm or refute…

Memory propagation in cells — and across generations: Newly folded RNAs bind stress-linked RBPs to assemble new condensates, passed on during cell division. Even daughter cells never facing the original stress can inherit the RNA structural memory – and its stress-adapted traits.

Why the memory fades eventually - as often seen in epigenetic inheritance: Two potential exits: Active reset: when conditions normalize, condensates dissolve, RBPs shift, RNA refolds. Passive fade: cells with stress-memory may grow slower, and are outcompeted over generations.

The model starts with RNA folding energy & a multistable landscape. Under stress, RNA can adopt a new shape—and if RNA-binding proteins “lock” it in, that shape becomes a molecular memory of the stress. Think Waddington’s epigenetic landscape—but for RNA folding energy valleys.

Trends in Biochemical Sciences

The heart of the hypothesis: copying RNA shape. Some RNAs can act as both template & catalyst, guiding new RNAs with the same sequence to fold the same way. RNA alone is unstable, but RBPs stabilize the template, & condensates boost RNA–RNA interactions—as a microreaction chamber

Qi Chen reposted

@cp-trendsbiochem.bsky.social

1 May 2025

Our 🌷 May 🌷 issue is online with a broad range of article topics and formats! In their Opinion article (on the cover, too!), @qichen-lab.bsky.social and colleagues describe the interactions between small ncRNAs and Toll-like receptors. Find the issue here: www.cell.com/trends/bioch...

bit.lyOptimized identification and characterization of small RNAs with PANDORA-seq - Nature ProtocolsThis Protocol describes optimized procedures for purification and sequencing of small noncoding RNAs from a variety of samples to characterize these diverse RNA species and map them to the parental RNAs from which they originate.

1 May 2025

Very glad to see our Sequential Activation Hypothesis highlighted on the cover @cp-trendsbiochem.bsky.social , linking small RNA-TLR interactions to autoimmune disease mechanisms.

Qi Chen@qichen-lab.bsky.social

How can abnormal small RNA biogenesis spark autoimmune disease? Our opinion @cp-trendsbiochem.bsky.social discuss a novel two-stage activation hypothesis that may explain why autoimmunity hits women harder, via small RNA-TLR7/8 interactions & augmented by autoantibodies. www.cell.com/trends/bioch...

Qi Chen reposted

Nature Protocols

@natprot.nature.com

8 Apr 2025

#NewNProt for #genomewide characterization of a diverse set of #smallnoncodingRNAs in cells and tissues

4 Apr 2025

We put together a step-by-step protocols for PANDORA-seq, now available in Nature Protocols @natprot.bsky.social , including the sample preparation for sperm, sperm heads; and the analyzing software SPORTS optimized for various types of small RNAs including tsRNAs, rsRNAs, and miRNAs. rdcu.be/egk1Z

This idea is driven by advanced sncRNA sequencing (e.g. PANDORA-seq), uncovering an expanding universe of tsRNA/rsRNA/ysRNA & more www.nature.com/articles/s41... These sncRNAs go beyond RNAi, adopting aptamer-like roles by binding TLR7/8 to shape immune responses www.jbc.org/article/S002...

Proud of @jianchengyu.bsky.social and the team for thinking fearlessly to put the ideas together!