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The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
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A single-cell resolved cell-cell communication model explains lineage commitment in hematopoiesis.

Megan K Rommelfanger1, Adam L MacLean1

  • 1Department of Quantitative and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA.

Development (Cambridge, England)
|December 22, 2021
PubMed
Summary

Cell fate decisions are influenced by environmental signals and cell-cell communication. Our study reveals how signaling impacts hematopoietic cell-fate choices, even breaking population symmetry.

Keywords:
BistabilityCell fateGene regulatory networkHematopoiesisMathematical modeling

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Area of Science:

  • * Systems Biology
  • * Developmental Biology
  • * Cellular Signaling

Background:

  • * Cell fate decisions are crucial for development and are influenced by external signals.
  • * Cell-cell communication significantly impacts intracellular gene regulatory networks, yet is often overlooked in models.
  • * The granulocyte-monocyte versus megakaryocyte-erythrocyte decision is a key hematopoietic process governed by the GATA1-PU.1 network.

Purpose of the Study:

  • * To develop a multiscale model integrating cell-cell communication into cell fate decisions.
  • * To investigate the impact of signaling and noise on the GATA1-PU.1 bistable system.
  • * To understand how cell communication influences symmetry breaking in cell populations.

Main Methods:

  • * Development of a multiscale modeling approach.
  • * Analysis of the GATA1-PU.1 gene regulatory network dynamics.
  • * Simulation of various cell communication topologies and noise levels.

Main Results:

  • * Subtle changes in signaling can lead to significant alterations in cell fate decisions across diverse communication networks.
  • * Cell-cell coupling via signaling can induce spontaneous symmetry breaking in initially homogeneous cell populations.
  • * Both intrinsic and extrinsic noise profoundly shape the cell fate decision landscape and transcriptional dynamics.

Conclusions:

  • * Cell-cell communication is a critical factor in cell fate determination, significantly modulating the outcomes of gene regulatory networks.
  • * Signaling-mediated cell coupling can drive population-level differentiation patterns.
  • * Noise plays a substantial role in the stochasticity of hematopoietic cell fate decisions.