Evidence map›Paper›PMID 41959100›Full record

ArticlebioRxiv : the preprint server for biology2026

Human neuromodulatory assembloids to study serotonin signaling and disease.

Sabina Kanton, Xiangling Meng, Chunyang Dong, Fikri Birey, Dong Wang, Noah Reis, Se-Jin Yoon, Ji-Il Kim, James P McQueen, Noriaki Sakai and 3 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Sabina KantonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3910-3480
Xiangling MengDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0002-3528-4037
Chunyang DongDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0002-4820-4454
Fikri BireyDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0003-2632-2764
Dong WangDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3314-2569
Noah ReisDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0002-7258-2463
Se-Jin YoonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8412-5991
Ji-Il KimDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0002-5710-7090
James P McQueenDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Noriaki SakaiDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0002-2918-6334
Seiji NishinoDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0003-3959-2886
John R HuguenardDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-6950-1191
Sergiu P PașcaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID 0000-0002-3216-3248

Funding

Gaining insight into psychiatric disease by engineering piece by piece the human brain in vitro.R01MH107800 · NIMH · STANFORD UNIVERSITY · PI PASCA, SERGIU · 2015 to 2024
$5.6M
NIMH NIH HHS R01 MH107800
6 · The paper itself

Abstract

Neuromodulators influence critical functions of the developing human brain and regulate behavioral states. Dysfunction of neuromodulatory systems is often involved in neuropsychiatric disease and many drugs for these conditions act on these signaling pathways. Recent advances in stem cell biology have made it possible to derive a wide range of cells across the developing human nervous system in regionalized organoids and to functionally integrate them into assembloids, however they currently do not systematically incorporate neuromodulation. Here, we generated human midbrain-hindbrain organoids (hMHO) from human induced pluripotent stem (hiPS) cells and fused them with human cortical organoids (hCO) to form neuromodulatory assembloids (hNMA). We focus on serotonin (5-hydroxytryptamine, 5-HT) as one key neuromodulator and found characteristic gene expression patterns and electrophysiological properties of serotonergic neurons (5-HT neurons) in the hMHO. In hNMA, 5-HT neurons projected into hCO, released 5-HT and modulated cortical network activity. To explore the applicability of this system in human disease, we studied 22q11.2 deletion syndrome (22q11.2DS), a common microdeletion associated with high risk for neuropsychiatric disease and defects in 5-HT signaling. We found aberrant 5-HT dynamics in hNMA from patient hiPS cell lines that were rescued by administration of a selective serotonin reuptake inhibitor (SSRI). Taken together, hNMA can be used to study human 5-HT dynamics and uncover disease phenotypes which could facilitate therapeutic development.

Identifiers

PMID41959100
PMCPMC13060871

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.