Joram Mooiweer
@jorammooiweer.bsky.social
Celiac disease mucosal immunity | Engineering intestine models | iPSCs, Organoids, T cells & organ-chips🔬| PhD candidate | Dept. of Genetics 🧬 | University Medical Center Groningen | University of Groningen (@rug.nl) |
📍Groningen, the Netherlands
📍Groningen, the Netherlands
When we align them with in vivo references:
- Organoids cluster closer to fetal intestine
- Intestine-on-chip clusters with pediatric/adult small intestine
- Transwells sit in between but don’t fully capture either extreme
So the chip looks most “adult gut–like” at the transcriptomic level!
- Organoids cluster closer to fetal intestine
- Intestine-on-chip clusters with pediatric/adult small intestine
- Transwells sit in between but don’t fully capture either extreme
So the chip looks most “adult gut–like” at the transcriptomic level!
November 19, 2025 at 10:13 PM
When we align them with in vivo references:
- Organoids cluster closer to fetal intestine
- Intestine-on-chip clusters with pediatric/adult small intestine
- Transwells sit in between but don’t fully capture either extreme
So the chip looks most “adult gut–like” at the transcriptomic level!
- Organoids cluster closer to fetal intestine
- Intestine-on-chip clusters with pediatric/adult small intestine
- Transwells sit in between but don’t fully capture either extreme
So the chip looks most “adult gut–like” at the transcriptomic level!
What we globally find:
🔹 Organoids
Strong developmental / fetal signatures
More embryonic patterning pathways
🔹 Transwells
More ECM remodeling, cell cycle, EMT-like features
🔹 Intestine-on-chip
Highest expression of digestion, nutrient transport & drug metabolism genes
🔹 Organoids
Strong developmental / fetal signatures
More embryonic patterning pathways
🔹 Transwells
More ECM remodeling, cell cycle, EMT-like features
🔹 Intestine-on-chip
Highest expression of digestion, nutrient transport & drug metabolism genes
November 19, 2025 at 10:13 PM
What we globally find:
🔹 Organoids
Strong developmental / fetal signatures
More embryonic patterning pathways
🔹 Transwells
More ECM remodeling, cell cycle, EMT-like features
🔹 Intestine-on-chip
Highest expression of digestion, nutrient transport & drug metabolism genes
🔹 Organoids
Strong developmental / fetal signatures
More embryonic patterning pathways
🔹 Transwells
More ECM remodeling, cell cycle, EMT-like features
🔹 Intestine-on-chip
Highest expression of digestion, nutrient transport & drug metabolism genes
Now the head-to-head showdown 🥊
We culture the same iPSC-derived epithelium in EM - DM+D+P as:
- 3D organoids
- 2D Transwell monolayers
- @emulatebio.bsky.social intestine-on-chip under flow
Then we compare their transcriptomes + map them onto in vivo small intestine data.
We culture the same iPSC-derived epithelium in EM - DM+D+P as:
- 3D organoids
- 2D Transwell monolayers
- @emulatebio.bsky.social intestine-on-chip under flow
Then we compare their transcriptomes + map them onto in vivo small intestine data.
November 19, 2025 at 10:13 PM
Now the head-to-head showdown 🥊
We culture the same iPSC-derived epithelium in EM - DM+D+P as:
- 3D organoids
- 2D Transwell monolayers
- @emulatebio.bsky.social intestine-on-chip under flow
Then we compare their transcriptomes + map them onto in vivo small intestine data.
We culture the same iPSC-derived epithelium in EM - DM+D+P as:
- 3D organoids
- 2D Transwell monolayers
- @emulatebio.bsky.social intestine-on-chip under flow
Then we compare their transcriptomes + map them onto in vivo small intestine data.
What about Transwells?
The EM–DM + D + P gradient lands perfectly in between:
- Keeps renewal / cell cycle pathways active
- Already shows enhanced digestion and xenobiotic metabolism
So you can balance “crypt-like” proliferation with “villus-like” function by cleverly combining media compositions
The EM–DM + D + P gradient lands perfectly in between:
- Keeps renewal / cell cycle pathways active
- Already shows enhanced digestion and xenobiotic metabolism
So you can balance “crypt-like” proliferation with “villus-like” function by cleverly combining media compositions
November 19, 2025 at 10:13 PM
What about Transwells?
The EM–DM + D + P gradient lands perfectly in between:
- Keeps renewal / cell cycle pathways active
- Already shows enhanced digestion and xenobiotic metabolism
So you can balance “crypt-like” proliferation with “villus-like” function by cleverly combining media compositions
The EM–DM + D + P gradient lands perfectly in between:
- Keeps renewal / cell cycle pathways active
- Already shows enhanced digestion and xenobiotic metabolism
So you can balance “crypt-like” proliferation with “villus-like” function by cleverly combining media compositions
Then we benchmark functionality using RNA-seq.
First organoids:
Compared to EM, the DM + D + P massively boosts genes for:
- Nutrient digestion
- Transporters
- Drug metabolism
These iPSC-derived cells can become strongly enterocyte-like!
First organoids:
Compared to EM, the DM + D + P massively boosts genes for:
- Nutrient digestion
- Transporters
- Drug metabolism
These iPSC-derived cells can become strongly enterocyte-like!
November 19, 2025 at 10:13 PM
Then we benchmark functionality using RNA-seq.
First organoids:
Compared to EM, the DM + D + P massively boosts genes for:
- Nutrient digestion
- Transporters
- Drug metabolism
These iPSC-derived cells can become strongly enterocyte-like!
First organoids:
Compared to EM, the DM + D + P massively boosts genes for:
- Nutrient digestion
- Transporters
- Drug metabolism
These iPSC-derived cells can become strongly enterocyte-like!
Next step: How can we mimic a crypt–villus axis in-vitro?
On Transwells we installed a growth factor gradient for this:
Basolateral: EM
Apical: DM + D _or_ DM + D + P
This indeed keeps a proliferative compartment and generates differentiated cells with tight junctions and good barrier properties.
On Transwells we installed a growth factor gradient for this:
Basolateral: EM
Apical: DM + D _or_ DM + D + P
This indeed keeps a proliferative compartment and generates differentiated cells with tight junctions and good barrier properties.
November 19, 2025 at 10:13 PM
Next step: How can we mimic a crypt–villus axis in-vitro?
On Transwells we installed a growth factor gradient for this:
Basolateral: EM
Apical: DM + D _or_ DM + D + P
This indeed keeps a proliferative compartment and generates differentiated cells with tight junctions and good barrier properties.
On Transwells we installed a growth factor gradient for this:
Basolateral: EM
Apical: DM + D _or_ DM + D + P
This indeed keeps a proliferative compartment and generates differentiated cells with tight junctions and good barrier properties.
At the cell type level we see:
- EM → lots of MKI67⁺ proliferative cells
- DM / DM + D → more enterocytes + goblet cells
- DM + D + P → differentiated epithelium with detectable enteroendocrine cells
(Paneth(-like) cells behave differently depending on the platform)
- EM → lots of MKI67⁺ proliferative cells
- DM / DM + D → more enterocytes + goblet cells
- DM + D + P → differentiated epithelium with detectable enteroendocrine cells
(Paneth(-like) cells behave differently depending on the platform)
November 19, 2025 at 10:13 PM
At the cell type level we see:
- EM → lots of MKI67⁺ proliferative cells
- DM / DM + D → more enterocytes + goblet cells
- DM + D + P → differentiated epithelium with detectable enteroendocrine cells
(Paneth(-like) cells behave differently depending on the platform)
- EM → lots of MKI67⁺ proliferative cells
- DM / DM + D → more enterocytes + goblet cells
- DM + D + P → differentiated epithelium with detectable enteroendocrine cells
(Paneth(-like) cells behave differently depending on the platform)
Totally psyched that our paper is out in @stemcellreports.bsky.social!
For human iPSC–based gut #NAMs, which platform would you trust to behave most like real intestinal tissue?
We put #organoids, Transwells and @emulatebio.bsky.social intestine-chip head to head.
Spoiler: the chip wins.
🧵&🔗👇
For human iPSC–based gut #NAMs, which platform would you trust to behave most like real intestinal tissue?
We put #organoids, Transwells and @emulatebio.bsky.social intestine-chip head to head.
Spoiler: the chip wins.
🧵&🔗👇
November 19, 2025 at 10:13 PM
Totally psyched that our paper is out in @stemcellreports.bsky.social!
For human iPSC–based gut #NAMs, which platform would you trust to behave most like real intestinal tissue?
We put #organoids, Transwells and @emulatebio.bsky.social intestine-chip head to head.
Spoiler: the chip wins.
🧵&🔗👇
For human iPSC–based gut #NAMs, which platform would you trust to behave most like real intestinal tissue?
We put #organoids, Transwells and @emulatebio.bsky.social intestine-chip head to head.
Spoiler: the chip wins.
🧵&🔗👇
Back to back commentaries in @natureportfolio.nature.com today. Clearly NAMs are causing a stir!
October 20, 2025 at 8:14 PM
Back to back commentaries in @natureportfolio.nature.com today. Clearly NAMs are causing a stir!
Every cell is a stem cell!
Even ‘terminal’ enterocytes can hit reset: Gut damage triggers a YAP/TAZ-driven fetal program → stress-proof “revival” stem cells → Lgr5⁺ CBC stem cells, rebuilding crypts from scratch and make organoids.
#StemCellPlasticity #Organoids #Gut
Even ‘terminal’ enterocytes can hit reset: Gut damage triggers a YAP/TAZ-driven fetal program → stress-proof “revival” stem cells → Lgr5⁺ CBC stem cells, rebuilding crypts from scratch and make organoids.
#StemCellPlasticity #Organoids #Gut
July 14, 2025 at 12:06 PM
Every cell is a stem cell!
Even ‘terminal’ enterocytes can hit reset: Gut damage triggers a YAP/TAZ-driven fetal program → stress-proof “revival” stem cells → Lgr5⁺ CBC stem cells, rebuilding crypts from scratch and make organoids.
#StemCellPlasticity #Organoids #Gut
Even ‘terminal’ enterocytes can hit reset: Gut damage triggers a YAP/TAZ-driven fetal program → stress-proof “revival” stem cells → Lgr5⁺ CBC stem cells, rebuilding crypts from scratch and make organoids.
#StemCellPlasticity #Organoids #Gut
Its honestly quite shocking.
Cancer cell lines are sub-optimal systems due to genomic instability, mutations and potentially strange phenotypes.
Thats known, but to see these anomalies quantified is a good moment to realize this once again.
#Celllines #ImmunoSky #Jurkat
Cancer cell lines are sub-optimal systems due to genomic instability, mutations and potentially strange phenotypes.
Thats known, but to see these anomalies quantified is a good moment to realize this once again.
#Celllines #ImmunoSky #Jurkat
July 4, 2025 at 6:29 AM
Its honestly quite shocking.
Cancer cell lines are sub-optimal systems due to genomic instability, mutations and potentially strange phenotypes.
Thats known, but to see these anomalies quantified is a good moment to realize this once again.
#Celllines #ImmunoSky #Jurkat
Cancer cell lines are sub-optimal systems due to genomic instability, mutations and potentially strange phenotypes.
Thats known, but to see these anomalies quantified is a good moment to realize this once again.
#Celllines #ImmunoSky #Jurkat
✨ Incredibly happy!!
To receive the 2025 Stimulering prize from the Dutch Coeliac Disease Association! 🙌
Huge Thanks to all NCV members for your trust💚
Excited to continue our mini-gut & gut-on-a-chip research at @umcgroningen.bsky.social 💚 #coeliakie #research #minigut
To receive the 2025 Stimulering prize from the Dutch Coeliac Disease Association! 🙌
Huge Thanks to all NCV members for your trust💚
Excited to continue our mini-gut & gut-on-a-chip research at @umcgroningen.bsky.social 💚 #coeliakie #research #minigut
July 2, 2025 at 9:28 PM
✨ Incredibly happy!!
To receive the 2025 Stimulering prize from the Dutch Coeliac Disease Association! 🙌
Huge Thanks to all NCV members for your trust💚
Excited to continue our mini-gut & gut-on-a-chip research at @umcgroningen.bsky.social 💚 #coeliakie #research #minigut
To receive the 2025 Stimulering prize from the Dutch Coeliac Disease Association! 🙌
Huge Thanks to all NCV members for your trust💚
Excited to continue our mini-gut & gut-on-a-chip research at @umcgroningen.bsky.social 💚 #coeliakie #research #minigut
Vascularized organoids!
Balancing BMP signaling enables co-differentiation of mesoderm + endoderm in a single spheroid → organ-specific endothelium + vascularized gut & lung organoids!
Ever increasing organoid complexity👏
#Organoids #StemCells
Balancing BMP signaling enables co-differentiation of mesoderm + endoderm in a single spheroid → organ-specific endothelium + vascularized gut & lung organoids!
Ever increasing organoid complexity👏
#Organoids #StemCells
June 30, 2025 at 9:36 PM
Vascularized organoids!
Balancing BMP signaling enables co-differentiation of mesoderm + endoderm in a single spheroid → organ-specific endothelium + vascularized gut & lung organoids!
Ever increasing organoid complexity👏
#Organoids #StemCells
Balancing BMP signaling enables co-differentiation of mesoderm + endoderm in a single spheroid → organ-specific endothelium + vascularized gut & lung organoids!
Ever increasing organoid complexity👏
#Organoids #StemCells
FDA 🤝 Organs-on-Chips
The @fda.gov recently published its Roadmap to Reducing Animal Testing in Preclinical Safety Studies. This is an exciting step forward in emphasizing the adoption of New Approach Methodologies (NAMs), focusing on human-derived in vitro and in silico models.
The @fda.gov recently published its Roadmap to Reducing Animal Testing in Preclinical Safety Studies. This is an exciting step forward in emphasizing the adoption of New Approach Methodologies (NAMs), focusing on human-derived in vitro and in silico models.
May 6, 2025 at 8:52 PM
FDA 🤝 Organs-on-Chips
The @fda.gov recently published its Roadmap to Reducing Animal Testing in Preclinical Safety Studies. This is an exciting step forward in emphasizing the adoption of New Approach Methodologies (NAMs), focusing on human-derived in vitro and in silico models.
The @fda.gov recently published its Roadmap to Reducing Animal Testing in Preclinical Safety Studies. This is an exciting step forward in emphasizing the adoption of New Approach Methodologies (NAMs), focusing on human-derived in vitro and in silico models.
Cheering for everyone standing up for science today!
👏👏👏
👏👏👏
March 7, 2025 at 8:41 PM
Cheering for everyone standing up for science today!
👏👏👏
👏👏👏
Seems obvious, but apparently, no one has really dived into it like this(?)👇
🧬 Epigenetic variation in iPSCs staged is mostly tied to genetic variation, but as cells differentiate, this dilutes out quickly: Cell type matters more than genetics.
#StemCells
www.nature.com/articles/s41...
🧬 Epigenetic variation in iPSCs staged is mostly tied to genetic variation, but as cells differentiate, this dilutes out quickly: Cell type matters more than genetics.
#StemCells
www.nature.com/articles/s41...
February 21, 2025 at 2:57 PM
Seems obvious, but apparently, no one has really dived into it like this(?)👇
🧬 Epigenetic variation in iPSCs staged is mostly tied to genetic variation, but as cells differentiate, this dilutes out quickly: Cell type matters more than genetics.
#StemCells
www.nature.com/articles/s41...
🧬 Epigenetic variation in iPSCs staged is mostly tied to genetic variation, but as cells differentiate, this dilutes out quickly: Cell type matters more than genetics.
#StemCells
www.nature.com/articles/s41...
“The world’s a shit show, so why not put 💩 on a chip?
Scientists created an iPSC-derived intestine-on-a-chip with fecal microbiota—uncovering epithelium-specific biomarkers & microbial factors linked to melanoma outcomes. Cutting-edge #OrganOnChip tech!
#ImmunoSky #MedSky”
Scientists created an iPSC-derived intestine-on-a-chip with fecal microbiota—uncovering epithelium-specific biomarkers & microbial factors linked to melanoma outcomes. Cutting-edge #OrganOnChip tech!
#ImmunoSky #MedSky”
February 14, 2025 at 9:46 AM
“The world’s a shit show, so why not put 💩 on a chip?
Scientists created an iPSC-derived intestine-on-a-chip with fecal microbiota—uncovering epithelium-specific biomarkers & microbial factors linked to melanoma outcomes. Cutting-edge #OrganOnChip tech!
#ImmunoSky #MedSky”
Scientists created an iPSC-derived intestine-on-a-chip with fecal microbiota—uncovering epithelium-specific biomarkers & microbial factors linked to melanoma outcomes. Cutting-edge #OrganOnChip tech!
#ImmunoSky #MedSky”
Its stories like this that makes me incredibly excited!
A gut immune–epithelial circuit regulating tolerance to food:
Goblet cell protein RELMβ disrupts tolerance by depleting microbiome-derived indoles needed for protective Tregs.
#microbiome #immunity #ImmunoSky
www.nature.com/articles/s41...
A gut immune–epithelial circuit regulating tolerance to food:
Goblet cell protein RELMβ disrupts tolerance by depleting microbiome-derived indoles needed for protective Tregs.
#microbiome #immunity #ImmunoSky
www.nature.com/articles/s41...
January 27, 2025 at 10:13 PM
Its stories like this that makes me incredibly excited!
A gut immune–epithelial circuit regulating tolerance to food:
Goblet cell protein RELMβ disrupts tolerance by depleting microbiome-derived indoles needed for protective Tregs.
#microbiome #immunity #ImmunoSky
www.nature.com/articles/s41...
A gut immune–epithelial circuit regulating tolerance to food:
Goblet cell protein RELMβ disrupts tolerance by depleting microbiome-derived indoles needed for protective Tregs.
#microbiome #immunity #ImmunoSky
www.nature.com/articles/s41...
TG2 (Transglutaminase 2) is responsible for the deamidation of gluten peptides, making them immunogenic antigens in the context of Celiac Disease - But what other functions does TG2 have?!
👇
TG2 drives epigenetic histone monoaminylation, regulating neural rhythmicity 🧠!
#Celiac
👇
TG2 drives epigenetic histone monoaminylation, regulating neural rhythmicity 🧠!
#Celiac
January 13, 2025 at 10:45 AM
TG2 (Transglutaminase 2) is responsible for the deamidation of gluten peptides, making them immunogenic antigens in the context of Celiac Disease - But what other functions does TG2 have?!
👇
TG2 drives epigenetic histone monoaminylation, regulating neural rhythmicity 🧠!
#Celiac
👇
TG2 drives epigenetic histone monoaminylation, regulating neural rhythmicity 🧠!
#Celiac
Time to log off for the holidays with a timelapse:
Intestinal organoid trying to resist the attack from CD8 T cells.
Happy holidays! 🎄🧑🎄
#ImmunoSky
Intestinal organoid trying to resist the attack from CD8 T cells.
Happy holidays! 🎄🧑🎄
#ImmunoSky
December 25, 2024 at 3:14 PM
Time to log off for the holidays with a timelapse:
Intestinal organoid trying to resist the attack from CD8 T cells.
Happy holidays! 🎄🧑🎄
#ImmunoSky
Intestinal organoid trying to resist the attack from CD8 T cells.
Happy holidays! 🎄🧑🎄
#ImmunoSky
Arrived. Excited for a 2-day Netherlands Organ-on-Chip Consortium gathering at the @hubrechtinstitute.bsky.social #Organoids #OrganOnChip #NOCI
December 18, 2024 at 8:48 AM
Arrived. Excited for a 2-day Netherlands Organ-on-Chip Consortium gathering at the @hubrechtinstitute.bsky.social #Organoids #OrganOnChip #NOCI
What do you find the most annoying piece of lab equipment and why is it the counting chamber?
#PhDchat #Immunosky
#PhDchat #Immunosky
December 5, 2024 at 3:11 PM
What do you find the most annoying piece of lab equipment and why is it the counting chamber?
#PhDchat #Immunosky
#PhDchat #Immunosky
The #intestine's dynamics (environment/movement/stiffness/flow) shapes stem cell fitness and function, shown here via PIEZO channels and is reflected in in-vitro models. So, are static 3D cultures sufficient? Could microphysiological systems #MPS #Organ-on-chip offer a better approach here?
December 1, 2024 at 10:22 AM
The #intestine's dynamics (environment/movement/stiffness/flow) shapes stem cell fitness and function, shown here via PIEZO channels and is reflected in in-vitro models. So, are static 3D cultures sufficient? Could microphysiological systems #MPS #Organ-on-chip offer a better approach here?