A systems biology pipeline identifies regulatory networks for stem cell engineering.
Nat Biotechnol
; 37(7): 810-818, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-31267104
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Biología de Sistemas
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Células Madre Pluripotentes Inducidas
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Ingeniería Celular
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Biotechnol
Asunto de la revista:
BIOTECNOLOGIA
Año:
2019
Tipo del documento:
Article