Induction of human pruriceptors from pluripotent stem cells via transcription factors.
Overview
- Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Mark Lebwohl Center for Neuroinflammation and Sensation, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Stem Cell Biology and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- AbbVie Deutschland GmbH & Co KG, Neuroscience Discovery, Knollstrasse, Ludwigshafen am Rhein, Germany
- AbbVie Inc., North Chicago, IL, USA
- AbbVie Cambridge Research Center, Cambridge, MA, USA
- Sanofi, Immunology and Inflammation Therapeutic Area, Cambridge, MA, USA
- Allen Discovery Center for Neuroimmune Interactions, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Abstract
Pruriception is crucial for defense against external stimuli but can lead to chronic pruritus, a debilitating condition affecting millions worldwide. Our understanding of the cellular and molecular mechanisms behind the sensation of itch has been hindered by the lack of functional human models. Here, we address this limitation by developing a protocol to generate induced pruriceptors (iPruriceptors) from human-induced pluripotent stem cells (iPSCs). We compared two differentiation approaches: a direct method via forced expression of transcription factors (TFs) in iPSCs and a 2-step process through expression of TFs in iPSC-derived neural crest cells (NCCs). The 2-step protocol proved superior in inducing a transcriptional program enriched for features of human pruriceptors. Our optimized protocol employs forced expression of NGN1 and ISL1 to drive differentiation from NCCs into pruriceptors, enhancing the expression of known pruritogen receptors such as IL31RA, which pairs with OSMR, and HRH1. The induction of this transcriptional program leads to functional maturation of iPruriceptors. Accordingly, iPruriceptors exhibit robust responses to itch stimuli and in vivo-like itch pharmacology such as treatment with ABT-317, a JAK1 inhibitor tool compound, similar to those targeting intensive pruritus in atopic dermatitis (AD). Importantly, iPruriceptors can be generated without viral vectors or safe-harbor gene editing, using a PiggyBac-based transfection method that simplifies scalability. Our protocol offers a robust platform for investigating itch biology, modeling chronic pruritus, and enabling high-throughput screening for therapeutic target discovery.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE329269, at NCBI GEO; found in “Data and code availability”
Data and code availability
Data reported in this paper will be shared by the lead contact upon request.
This paper does not report original code.
RNA sequencing data have been deposited in the Gene Expression Omnibus (GEO) repository with accession number GSE329269 (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 10 keywords, 7 MeSH terms, 2 funders, 72 references, 35 RRIDs.
Cite
This paper
Iriki, H., Hu, R., Li, X., Baljinnyam, E., Habich, C., Imanishi, I., Miller, L. N., Chegireddy, K., Malik, L. I., Yassky, D., Kübler, R., Heul, A. V., Smith, K. M., Reinhardt, P., Goedken, E. R., Kim, B. S., & Marro, S. G. (2026). Induction of human pruriceptors from pluripotent stem cells via transcription factors. Stem cell reports, 21(8), 103004. https://
BibTeX
@article{iriki2026induct
author = {Iriki, Hisato and Hu, Ruiqi and Li, Xu and Baljinnyam, Erdene and Habich, Carina and Imanishi, Ichiro and Miller, Loan N and Chegireddy, Kavya and Malik, Laraib Iqbal and Yassky, Daniel and Kübler, Raphael and Heul, Aaron Ver and Smith, Kathleen M and Reinhardt, Peter and Goedken, Eric R and Kim, Brian S and Marro, Samuele G},
title = {{Induction of human pruriceptors from pluripotent stem cells via transcription factors}},
journal = {Stem cell reports},
year = {2026},
month = jul,
volume = {21},
number = {8},
pages = {103004},
publisher = {Elsevier},
issn = {2213-6711},
doi = {10.1016/
url = {https://
pmid = {42425092},
pmcid = {PMC13476876}
}
RIS
TY - JOUR
AU - Iriki, Hisato
AU - Hu, Ruiqi
AU - Li, Xu
AU - Baljinnyam, Erdene
AU - Habich, Carina
AU - Imanishi, Ichiro
AU - Miller, Loan N
AU - Chegireddy, Kavya
AU - Malik, Laraib Iqbal
AU - Yassky, Daniel
AU - Kübler, Raphael
AU - Heul, Aaron Ver
AU - Smith, Kathleen M
AU - Reinhardt, Peter
AU - Goedken, Eric R
AU - Kim, Brian S
AU - Marro, Samuele G
TI - Induction of human pruriceptors from pluripotent stem cells via transcription factors
T2 - Stem cell reports
J2 - Stem Cell Reports
PY - 2026
DA - 2026/
VL - 21
IS - 8
SP - 103004
SN - 2213-6711
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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