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
-
- Cell Proliferation
- Cell Engineering*
- Gene Regulatory Networks
- Systems Biology/methods*
- Algorithms
- Humans
- Antigens, CD34/genetics
- Antigens, CD34/metabolism
- Mice
- Animals
- Computational Biology/methods
- Receptor, ErbB-4/metabolism
- Erythropoiesis
- Zebrafish
- Cell Differentiation
- Erythrocytes
- Gene Expression Regulation
- Signal Transduction
- Induced Pluripotent Stem Cells/physiology*
- Cell Lineage
- Flow Cytometry
- Hematopoietic Stem Cells/metabolism*
- PubMed
- 31267104 Full text @ Nat Biotechnol.
Citation
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. (2019) A systems biology pipeline identifies regulatory networks for stem cell engineering. Nature Biotechnology. 37:810-818.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping