# Generation of an iPSC-derived alveolar rhabdomyosarcoma cell line during directed endothelial differentiation

## TL;DR

This paper describes a method to create a cell model of alveolar rhabdomyosarcoma using iPSCs and an oncofusion protein during endothelial differentiation.

## Contribution

A novel protocol for generating iPSC-derived alveolar rhabdomyosarcoma cells during endothelial differentiation using PAX3::FOXO1.

## Key findings

- ARMS tumors can originate from non-myogenic cells like endothelial progenitors.
- Enforced P3F expression during differentiation leads to aggressive myogenic tumor formation.
- The iARMS model enables study of P3F's role in tumor transformation.

## Abstract

Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue sarcoma typically driven by the oncofusion protein PAX3::FOXO1 (P3F). Despite ARMS tumor histology and transcriptome resembling skeletal muscle, these tumors arise in areas devoid of skeletal muscle, indicating that non-myogenic cells can give rise to ARMS. Our lab demonstrated that endothelial progenitors are a cell of origin for rhabdomyosarcoma. Here we provide a protocol for generating iPSC-derived alveolar rhabdomyosarcoma cells (iARMS) during endothelial directed differentiation through enforced expression of P3F. This model allows for dissection of how P3F mediates transformation of endothelial progenitors into aggressive myogenic tumors.