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A High-throughput Cell Microarray Platform for Correlative Analysis of Cell Differentiation and Traction Forces

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Morfología celular y expresión génica: seguimiento de cambios y complementariedad a través del tiempo y las líneas

Vanille Lejal¹, David Rouquié², Olivier Taboureau¹

¹Université Paris Cité, Inserm U1133, CNRS UMR 8251, Paris, France.

Toxicology and applied pharmacology

|August 22, 2025

Resumen

Los datos de Cell Painting y L1000 revelan cómo la exposición química altera la estructura celular y la expresión génica. Estos métodos complementarios mejoran el descubrimiento de fármacos al vincular los cambios morfológicos con los efectos moleculares.

Palabras clave:

Inhibidores de la CDK Líneas celulares Pintura de las células Evaluación del riesgo químico Inhibidores de la HDAC Se trata de:Exposición temporal

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Área de la Ciencia:

Biología química
La genómica
Imágenes celulares

Sus antecedentes:

El descubrimiento de fármacos requiere integrar el conocimiento del objetivo, los ensayos funcionales y los datos multiómicos.
La interacción entre los cambios inducidos por químicos en la morfología celular y la expresión génica a lo largo del tiempo y a través de las líneas celulares no se comprende bien.

Objetivo del estudio:

Investigar la relación entre los cambios en la morfología celular (Cell Painting) y la desregulación de la expresión génica (L1000) tras la exposición química.
Explorar estas relaciones a través de diferentes líneas celulares y puntos de tiempo.

Principales métodos:

Análisis de datos de Cell Painting y L1000 para 106 compuestos a través de líneas celulares U2OS, A549 y MCF7 a las 6, 24 y 48 horas.
Utilizó el análisis de la red de coexpresión génica ponderada (WGCNA) y el análisis de enriquecimiento para identificar correlaciones.

Principales resultados:

Se observaron diferencias significativas, específicas del tiempo y de la línea celular, en la organización de la estructura celular a través de Cell Painting.
Las respuestas transcriptómicas mostraron menos variabilidad en comparación con los cambios morfológicos.
Enlaces identificados entre la morfología celular y la desregulación génica de compuestos con acciones biológicas similares (por ejemplo, inhibidores de HDAC y CDK).

Conclusiones:

La pintura celular proporciona patrones distintos de respuesta celular a la exposición química.
Los datos de Cell Painting y L1000 ofrecen información complementaria sobre los efectos de los compuestos.
Estos enfoques integrados pueden mejorar el descubrimiento de fármacos y la evaluación de riesgos químicos al conectar los cambios fenotípicos y moleculares.