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Microenvironmental Sensing by Fibroblasts Controls Macrophage Population Size

Zhou X., Franklin R. et al. (BioRxiv) DOI: 10.1101/2022.01.18.476683

Microenvironmental Sensing by Fibroblasts Controls Macrophage Population Size


  • Macrophage

  • Fibroblast

  • Population size control

Main Findings

The proliferation of macrophages and fibroblast is limited by different factors in vitro. While fibroblast growth is largely space availability, macrophages are more dependent on the availability of the growth factor CSF1. However, fibroblast produce CSF1 for macrophages and therefore, macrophages become indirectly space-dependent in co-culture systems.

The transcriptome of fibroblast cultured at different densities was investigated based on which density-dependent genes were identified and this knowledge was used to develop an algorithm that can be applied on scRNA datasets to estimate the density of cells in the datasets. This algorithm correctly calculated that lung cells from patients with pulmonary fibrosis would have a higher density than cells from healthy controls.

While both Hippo and TGF- β pathways were found to be regulating several density-dependent genes, Hippo signalling through YAP1 and TEAD were regulating density-dependent expression of CSF1. Furthermore, the expression of YAP1 was linked to the mechanical pressure exerted by cytoskeleton on the nucleus.

The effect of other environmental factors such as oxidative stress, glucose or glutamine deprivation or osmotic pressure were also investigated. The changes in growth factor expression upon several different environmental stimuli were correlated.


  • As the authors also acknowledge, most of the studies are done in vitro. Thus, it remains to be elucidated if the same mechanisms are relevant in vivo.

  • Quantification of IHC images would make the data even more convincing.

  • It would be interesting to see if the expression of CSF-1 is changing in response to any of the other tested environmental stimuli.


Macrophages and fibroblast have a coordinated population size control and macrophages are indirectly dependent on space availability because of their dependency on CSF1 produced by fibroblast.

These mechanisms could potentially be important for tissue homeostasis and repair.


Reviewed by Zerina Kurtovic as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai, the Kennedy Institute of Rheumatology and the Oxford Centre for Immuno-Oncology  (OXCIO) (University of Oxford, GB) and Karolinska Institute’s Center for Infectious Medicine (CIM) & Center for Molecular Medicine (CMM). You can follow her on Twitter.

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