Epigenetic memory of colitis promotes tumour growth - Nature Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate...

A little late to Bluesky but my postdoc work w/ @jbuenrostro.bsky.social now out in @nature.com
"Epigenetic memory of colitis promotes tumour growth"
www.nature.com/articles/s41...

We wanted to understand how transient inflammation can create an increase in cancer risk, even after full recovery 🧵

Lead by @snaga13.bsky.social, special thanks to Omer Yilmaz, David Breault and Mike Greenberg for their collaboration and an additional thanks to @cancergrand.bsky.social @igvfconsortium.bsky.social for support

The epigenome "remembers" inflammation and primes stem cells for cancer
@snaga13.bsky.social @nature.com @jbuenrostro.bsky.social @harvard.edu
www.nature.com/articles/s41...
www.nature.com/articles/d41...

This reframes how we think about cancer.

It is not just about having the right mutation in the right cell type. It is also about a cell's prior experiences.

In short, a cell’s history, written into its epigenome, can shape how disease unfolds.

We then introduced an oncogenic mutation.

What we saw was striking: cells with prior inflammatory memory formed larger tumors, effectively lowering the threshold for transformation.

Same mutation, different outcome depending on the cell’s past experiences.

The answer was yes! Using a new method (SHARE-TRACE), we found that inflammation rewires the epigenome of stem cells that persists long after recovery.

These changes are clonal, encoded through TF activity, and stabilized over time by DNA methylation, forming a durable molecular memory.

To test this, we turned to a mouse model of chronic colitis, where we could control when inflammation happens, when it resolves, and what comes next.

This gave us a clean way to ask: does past inflammation leave a lasting imprint on cells?

Epigenome The term epigenome is derived from the Greek word epi which literally means "above" the genome.

In my lab, we are driven by the simple idea: epigenomes are drivers of disease.

We asked whether inflammation leaves lasting epigenetic changes that quietly predispose cells to become cancerous.

The epigenome: genome.gov/genetics-glo...

Epigenetic memory of colitis promotes tumour growth - Nature Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate...

It’s well known that inflammation increases cancer risk, but how?

The answer: the epigenome "remembers" inflammation and primes stem cells for cancer.

Here is our paper: nature.com/articles/s41...
And a special shoutout to the lead author
@snaga13.bsky.social

A 🧵

How inflammation may prime the gut for cancer A study in mice suggests that even intestinal cells that appear healthy may hold epigenetic “memories” of earlier bouts of inflammation that can promote colon cancer later in life.

Chronic gut inflammation leaves behind “molecular scars” that may raise the risk for developing cancer, according to a new study showing that epigenetic memory of colitis, along with a cancer-promoting mutation, can accelerate tumor growth in mice. @jbuenrostro.bsky.social

Free webinar featuring Jay Shendure and Jason Buenrostro. Charting Cellular Futures: Lineage Recording & Regulatory Network Insights. March 31 2pm ET. Register www.jax.org/GenomeTechDev26/

Coming Soon: March 31 @2pm ET. 📅
Charting Cellular Futures: Lineage Recording & Regulatory Network Insights.
Free webinar featuring @jshendure.bsky.social and @jbuenrostro.bsky.social.

Register www.jax.org/GenomeTechDev26/
🧪🧪💻

Jason Buenrostro stands behind a podium speaking to an audience.

Broad has launched the Biology of Adversity Project, led by
@jbuenrostro.bsky.social a 2023 @macfound.org fellow, to uncover how adverse life experiences can inflict molecular “scars” in the genome and body and increase risk of heart disease and other disorders. Learn more: broad.io/BAP

This is a great opportunity. Apply and join our community!
academicjobsonline.org/ajo/jobs/30714

DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells The extracellular space is a critical environment for discriminating self versus non-self nucleic acids and initiating the appropriate immune responses through signaling cascades to relay information ...

We’re excited to report work led by postdoc Jennifer Porat in the lab, finding that DNA accumulates on the surface of living cells and that the secreted extracellular protein DNASE1L3 can modulate its levels on B and T cells. With a new twist for ATAC-seq as well www.biorxiv.org/content/10.1...

Induction of menstruation in mice reveals the regulation of menstrual shedding During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this co...

I’m thrilled to share my postdoc work and the first paper from the McKinley Lab! 🎉
@karalmckinley.bsky.social
We built the first transgenic model of menstruation in mice.
We used it to uncover how the endometrium organizes and sheds during menstruation. 🧪
www.biorxiv.org/content/10.1...
🧵

Induction of menstruation in mice reveals the regulation of menstrual shedding During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this co...

Congratulations @karalmckinley.bsky.social & lab on their groundbreaking recent preprint establishing + characterizing a chemically inducible model of menstruation in mouse:

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

My jaw dropped when I heard this presented earlier this year. Incredible.

Jason Buenrostro named core institute member at Broad An expert in epigenetics and longtime member of the Broad community, Buenrostro will focus on how life experiences can alter the epigenome and increase risk of disease.

Leading epigenetics researcher and longtime Broad member
@jbuenrostro.bsky.social has been named core institute member of the Broad. His lab will study how cells change in response to life experiences, and how those alterations affect health and disease.

One last thing - I am on the job market! My lab will extend this approach to decode resilient chromatin: adaptations in proteins/DNA that allow for survival in harsh environments. These hold the 🔑 to designing cells that thrive under stress, esp. as we push the limits of where we take them ❄️🚀🪐🌱9/9

Engineered histones reshape chromatin in human cells Histone proteins and their variants have been found to play crucial and specialized roles in chromatin organization and the regulation of downstream gene expression; however, the relationship between ...

Huge thanks to all co-authors and the inimitable @jbuenrostro.bsky.social for supporting this new direction - I got to think about evolution, engineering, chromatin biophysics, and modeling during the course of this project. For more, check out the preprint: www.biorxiv.org/content/10.1... 8/9

Excited to share my postdoc work, out on bioRxiv today! Histones package DNA into nucleosomes to form the building blocks of chromatin, but how modular and programmable is this system? 1/9

Had a super week filled with great science, curiosity and discussions at this year's Gordon Research Conference on Human genetics and genomics. Also fun when you get to give a talk the same day as your postdoc advisor @jbuenrostro.bsky.social

The 2025 Freeman Hrabowski Scholars | HHMI Freeman Hrabowski Scholars are outstanding early career faculty who have the potential to become leaders in their research fields.

Honored to be an HHMI FHS! Grateful to brilliant colleagues who push me to think deeply, and to my students whose curiosity & energy make the lab a joy.

My grad advisor said in genetic screens, you don’t get what you want—you get what you deserve. Hope we are deserving

www.hhmi.org/programs/fre...

Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation Microscopy and genomics are used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. Here, we describe expansion i...

Epigenetics Update - Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation bit.ly/4jtXApb

Jason D. Buenrostro (MIT/Harvard) reporting in Science

#Epigenetics #Chromatin
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Gain deeper insights into gene regulation; epigenometech.com

Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation Microscopy and genomics are used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. Here, we describe expansion i...

@science.org Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation | Science www.science.org/doi/10.1126/...
@jbuenrostro.bsky.social @eboyden3.bsky.social + al @broadinstitute.org @harvard.edu
#ExIGS #Chromatin #Lamin #Progeria #Aging #ExpansionMicroscopy

A new combination technique enables DNA sequencing and high-resolution imaging in intact cells — offering new insights into progeria and aging. broad.io/expansion-in-situ @jbuenrostro.bsky.social

A lot of fun teaming up with Hsin and Howard on this, with key contributions from @ruochiz.bsky.social, @zchiang.bsky.social, and @jbuenrostro.bsky.social on the tech dev and @mattjones.bsky.social, Natasha Weiser, and Paul Mischel on the ecDNA analysis. (5/5)

Disease diagnostics using machine learning of B cell and T cell receptor sequences Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune system’s own record of antigen ...

Disease diagnostics using machine learning of B cell and T cell receptor sequences

www.science.org/doi/10.1126/...

TL;DR: BCRs ARE ALL YOU NEED!

(Well actually .... keep reading) 1/

We’d like to thank our collaborators in the Yilmaz and Breault labs, and PROSPECT @cancerresearchuk.org / NCI for their support. Find out about binding partners, drugging AP-1, the new tools we made and more here at our pre-print: tinyurl.com/ColitisNagar... (14/14)

New to bluesky, but I’m excited to share my work over the last few years with @jbuenrostro.bsky.social! Chronic inflammation creates an epigenetic memory in colonic stem cells, priming them for tumor growth: tinyurl.com/ColitisNagar.... Here’s a walkthrough of what we found (🧵)