Transcriptomic profiling of human iPSC-derived Schwann-like cells reveals NF2-regulated gene regulatory networks
Abstract
Schwann cells are vital to development and maintenance of the peripheral nervous system, and their dysfunction has been implicated in a range of neurological and neoplastic disorders, including NF2 -related schwannomatosis ( NF2 -SWN). We have developed a human induced pluripotent stem cells (hiPSCs) model for the study of Schwann-like cell differentiation in health and disease. We performed sequence-based transcriptomics, immunofluorescence-based morphological analysis, and CRISPR-Cas9-based validation of differentiation from hiPSCs derived Schwann cell precursors (SCPs) to terminally differentiated Schwann-like cells (SLCs) representing 6 distinct stages of development across a period of 31 days. To further validate our findings, we performed integrated, cross-species analyses at bulk and single cell resolution. Our hiPSCs model of Schwann cell development shared overlapping gene expression signatures with human amniotic mesenchymal stem cell (hAMSCs) derived SLCs and in vivo mouse models but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we have identified gene co-expression modules that are dynamically regulated during hiPSCs to SLCs differentiation associated with ear and neural development, cell fate determination, the NF2 gene, and extracellular matrix (ECM) organization. Through integrated analysis of multiple datasets and genetic disruption of NF2 via CRISPR-Cas9 gene editing in hiPSC derived SCPs, we have identified transcriptomic signatures suggesting a series of novel ECM associated genes potentially regulated by Merlin, providing a hypothesis-generating framework for future functional studies. The hiPSC model generated in this study further provides a system for studying NF2-regulated gene expression throughout Schwann-like cell development in the context of widely available data on iPSC Schwann cells and rare diseases that lack effective treatments such as NF2 -SWN.
Versions
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BibTeX
@article{lazaro2026transcriptomic,
title = {{Transcriptomic profiling of human iPSC-derived Schwann-like cells reveals NF2-regulated gene regulatory networks}},
author = {Olivia Lazaro and Sihong Li and Jacob S. Smiley and William Carter and Austin House and Oluwamayowa Awosika and Sylvia Robertson and Angela K. Haskell and Raven Dance Hinkel and Brooke E. Hickey and Steven P. Angus and D. Wade Clapp and Abdul Qadir Syed and Travis S. Johnson and Steven D. Rhodes},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-69205-y},
url = {https://www.nature.com/articles/s41598-026-69205-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptomic profiling of human iPSC-derived Schwann-like cells reveals NF2-regulated gene regulatory networks
AU - Olivia Lazaro
AU - Sihong Li
AU - Jacob S. Smiley
AU - William Carter
AU - Austin House
AU - Oluwamayowa Awosika
AU - Sylvia Robertson
AU - Angela K. Haskell
AU - Raven Dance Hinkel
AU - Brooke E. Hickey
AU - Steven P. Angus
AU - D. Wade Clapp
AU - Abdul Qadir Syed
AU - Travis S. Johnson
AU - Steven D. Rhodes
PY - 2026
DA - 2026/10/10
JO - Scientific Reports
DO - 10.1038/s41598-026-69205-y
UR - https://www.nature.com/articles/s41598-026-69205-y
AB - Schwann cells are vital to development and maintenance of the peripheral nervous system, and their dysfunction has been implicated in a range of neurological and neoplastic disorders, including NF2 -related schwannomatosis ( NF2 -SWN). We have developed a human induced pluripotent stem cells (hiPSCs) model for the study of Schwann-like cell differentiation in health and disease. We performed sequence-based transcriptomics, immunofluorescence-based morphological analysis, and CRISPR-Cas9-based validation of differentiation from hiPSCs derived Schwann cell precursors (SCPs) to terminally differentiated Schwann-like cells (SLCs) representing 6 distinct stages of development across a period of 31 days. To further validate our findings, we performed integrated, cross-species analyses at bulk and single cell resolution. Our hiPSCs model of Schwann cell development shared overlapping gene expression signatures with human amniotic mesenchymal stem cell (hAMSCs) derived SLCs and in vivo mouse models but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we have identified gene co-expression modules that are dynamically regulated during hiPSCs to SLCs differentiation associated with ear and neural development, cell fate determination, the NF2 gene, and extracellular matrix (ECM) organization. Through integrated analysis of multiple datasets and genetic disruption of NF2 via CRISPR-Cas9 gene editing in hiPSC derived SCPs, we have identified transcriptomic signatures suggesting a series of novel ECM associated genes potentially regulated by Merlin, providing a hypothesis-generating framework for future functional studies. The hiPSC model generated in this study further provides a system for studying NF2-regulated gene expression throughout Schwann-like cell development in the context of widely available data on iPSC Schwann cells and rare diseases that lack effective treatments such as NF2 -SWN.
SN - 2045-2322
ER -