Gene regulatory networks (GRNs) are groups of genes that encode transcription factors responsible for gene expression changes during cell fate specification. One common GRN topology in lineage specification consists of two mutually repressive genes. A well-studied example of such a network involves GATA1 and PU.1 – two transcription factors that regulate the binary choice of myeloid progenitors to enter either the megakaryocyte-erythroid (ME) or the granulocyte-monocyte (GM) lineage. It has been proposed that random fluctuations of GATA1 and PU.1 determine cell fate, but more recent data has questioned whether these fluctuations are sufficient and have highlighted a role for cell-cell signalling. In this Issue, Megan Rommelfanger and Adam MacLean use a multiscale model that combines a stochastic cell-cell communication motif (described by a Poisson process) upstream of the deterministic dynamics of the GATA1/PU.1 GRN. Using the model, the authors record the impact of altering the mode of signalling (positive or negative feedback), the strength of cell connections and the spatial organisation of connections. In all cases, the cells reach a bistable state (ME or GM fate), but minor changes in these parameters have pronounced effects on the cell fate outcomes of the population. This model explains how the addition of cell-cell communication changes cell fate decisions from deterministic to probabilistic, and how a homogenous population can be transformed into a heterogenous bistable population, in line with experimental data. Together, these data highlight the importance of cell extrinsic signals in lineage specification.
Cell fate specification: a multiscale model
- Split-screen
- Views Icon Views
-
Article Versions Icon
Versions
- Version of Record 22 December 2021
- Share Icon Share
-
Tools Icon
Tools
- Search Site
Cell fate specification: a multiscale model. Development 15 December 2021; 148 (24): e148_e2404. doi:
Download citation file:
Advertisement
Cited by
About us

Our publisher, The Company of Biologists, turns 100 this year. Read about the history of the Company and find out what Sarah Bray, our Chair of the Board of Directors, has to say.
Biologists @ 100 - join us in Liverpool in March 2025

We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register by 28 February 2025 to join us in March 2025 in Liverpool, UK.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues

Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology

In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
In preprints
Did you know that Development publishes perspectives on recent preprints? These articles help our readers navigate the ever-growing preprint literature. We welcome proposals for ‘In preprints’ articles, so please do get in touch if you’d like to contribute.