University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Molecular Medicine; Program in Systems Biology

Publication Date

2020-12-21

Document Type

Article Preprint

Disciplines

Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Systems Biology

Abstract

“Community effect” conventionally describes differentiation occurring only when enough cells help their local (micrometers-scale) neighbors differentiate. Although new community effects are being uncovered for myriad differentiations, macroscopic-scale community effects - fates of millions of cells all entangled across centimeters - remain elusive. We found that differentiating mouse Embryonic Stem (ES) cells that are scattered as individuals over many centimeters form one macroscopic entity via long-range communications. The macroscopic population avoids extinction only if its centimeter-scale density is above a threshold value. Single-cell-level measurements, transcriptomics, and mathematical modeling revealed that this “global community effect” occurs because differentiating ES-cell populations secrete, accumulate, and sense survival-promoting factors, including FGF4, that diffuse over many millimeters and activate Yap1-induced survival mechanisms. Only above-threshold-density populations accumulate above-threshold-concentrations of factors required to survive. We thus uncovered a previously overlooked, large-scale cooperation that underlies ES-cell differentiation. Tuning such large-scale cooperation may enable constructions of macroscopic, synthetic multicellular structures.

Keywords

Systems Biology, embryonic stem cell differentiation, Community effect

Rights and Permissions

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

DOI of Published Version

10.1101/2020.12.20.423651

Source

bioRxiv 2020.12.20.423651; doi: https://doi.org/10.1101/2020.12.20.423651. Link to preprint on bioRxiv.

Comments

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

Journal/Book/Conference Title

bioRxiv

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Share

COinS