Adult mouse fibroblasts retain organ-specific transcriptomic identity

Area of Science:

• Cell Biology
• Developmental Biology
• Genomics

Background:

• Fibroblasts are crucial tissue-resident cells involved in homeostasis and disease.
• Recent research highlights significant transcriptomic diversity among fibroblasts across different organs.
• Understanding the origins of this heterogeneity is key to comprehending fibroblast function.

Purpose of the Study:

• To investigate the basis of interorgan fibroblast heterogeneity.
• To determine if fibroblasts maintain organ-specific gene expression signatures.
• To explore the functional implications of these signatures in disease modulation.

Main Methods:

• Comparative transcriptomic analysis of murine fibroblasts from multiple organs (tail, skin, lung, liver, heart, kidney, gonads).
• Assessment of gene expression stability in culture, bioengineered tissues, and ectopic transplants.
• Functional studies involving targeted knockdown of organ-specific transcription factors.

Main Results:

• Murine fibroblasts exhibit distinct organ-specific transcriptome signatures reflecting their embryonic origins.
• These signatures are established during embryonic development and largely preserved in various experimental conditions.
• Knockdown of key transcription factors impacts fibroblast functions, particularly those related to fibrosis and inflammation.

Conclusions:

• Adult fibroblasts inherit and maintain embryonic gene expression signatures specific to their organ of origin.
• This inherent heterogeneity contributes to fibroblast function and tissue-specific responses.
• Knowledge of these tissue-specific signatures can inform precise, organ-targeted therapeutic strategies for fibrotic diseases.