PUBLICATION

A systems biology pipeline identifies regulatory networks for stem cell engineering

Authors
Kinney, M.A., Vo, L.T., Frame, J.M., Barragan, J., Conway, A.J., Li, S., Wong, K.K., Collins, J.J., Cahan, P., North, T.E., Lauffenburger, D.A., Daley, G.Q.
ID
ZDB-PUB-191108-36
Date
2019
Source
Nature Biotechnology   37: 810-818 (Journal)
Registered Authors
North, Trista
Keywords
none
MeSH Terms
  • Algorithms
  • Animals
  • Antigens, CD34/genetics
  • Antigens, CD34/metabolism
  • Cell Differentiation
  • Cell Engineering*
  • Cell Lineage
  • Cell Proliferation
  • Computational Biology/methods
  • Erythrocytes
  • Erythropoiesis
  • Flow Cytometry
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Hematopoietic Stem Cells/metabolism*
  • Humans
  • Induced Pluripotent Stem Cells/physiology*
  • Mice
  • Receptor, ErbB-4/metabolism
  • Signal Transduction
  • Systems Biology/methods*
  • Zebrafish
PubMed
31267104 Full text @ Nat Biotechnol.
Abstract
A major challenge for stem cell engineering is achieving a holistic understanding of the molecular networks and biological processes governing cell differentiation. To address this challenge, we describe a computational approach that combines gene expression analysis, previous knowledge from proteomic pathway informatics and cell signaling models to delineate key transitional states of differentiating cells at high resolution. Our network models connect sparse gene signatures with corresponding, yet disparate, biological processes to uncover molecular mechanisms governing cell fate transitions. This approach builds on our earlier CellNet and recent trajectory-defining algorithms, as illustrated by our analysis of hematopoietic specification along the erythroid lineage, which reveals a role for the EGF receptor family member, ErbB4, as an important mediator of blood development. We experimentally validate this prediction and perturb the pathway to improve erythroid maturation from human pluripotent stem cells. These results exploit an integrative systems perspective to identify new regulatory processes and nodes useful in cell engineering.
Errata / Notes
This article is corrected by ZDB-PUB-220906-162 .
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping