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Cited by 314

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling

Open access
Wang, Linlin, Schulz, Thomas C., Sherrer, Eric S., Dauphin, Derek S., Shin, Soojung, Nelson, Angelique M., Ware, Carol B., Zhan, Mei, Song, Chao-Zhong, Chen, Xiaoji, Brimble, Sandii N., McLean, Amanda, Galeano, Maria J., Uhl, Elizabeth W., D'Amour, Kevin A., Chesnut, Jonathan D., Rao, Mahendra S., Blau, C. Anthony, Robins, Allan J.·2007·Blood

Abstract

Despite progress in developing defined conditions for human embryonic stem cell (hESC) cultures, little is known about the cell-surface receptors that are activated under conditions supportive of hESC self-renewal. A simultaneous interrogation of 42 receptor tyrosine kinases (RTKs) in hESCs following stimulation with mouse embryonic fibroblast (MEF) conditioned medium (CM) revealed rapid and prominent tyrosine phosphorylation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R); less prominent tyrosine phosphorylation of epidermal growth factor receptor (EGFR) family members, including ERBB2 and ERBB3; and trace phosphorylation of fibroblast growth factor receptors. Intense IGF1R and IR phosphorylation occurred in the absence of MEF conditioning (NCM) and was attributable to high concentrations of insulin in the proprietary KnockOut Serum Replacer (KSR). Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, while disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis. A simple defined medium containing an IGF1 analog, heregulin-1β (a ligand for ERBB2/ERBB3), fibroblast growth factor-2 (FGF2), and activin A supported long-term growth of multiple hESC lines. These studies identify previously unappreciated RTKs that support hESC proliferation and self-renewal, and provide a rationally designed medium for the growth and maintenance of pluripotent hESCs.

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Metadata

Authors
Wang, L., Schulz, T. C., Sherrer, E. S., Dauphin, D. S., Shin, S., Nelson, A. M., Ware, C. B., Zhan, M., Song, C.-Z., Chen, X., Brimble, S. N., McLean, A., Galeano, M. J., Uhl, E. W., D'Amour, K. A., Chesnut, J. D., Rao, M. S., Blau, C. A., & Robins, A. J.
Venue
Blood
Published
2007-12-01
Volume
110
Issue
12
Pages
4111-4119
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2040914220
Cited by
314
References
36
FWCI
10.54
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling. https://app.cochat.ai/papers/10.1182/blood-2007-03-082586
The paper
Wang, L., Schulz, T. C., Sherrer, E. S., Dauphin, D. S., Shin, S., Nelson, A. M., Ware, C. B., Zhan, M., Song, C.-Z., Chen, X., Brimble, S. N., McLean, A., Galeano, M. J., Uhl, E. W., D'Amour, K. A., Chesnut, J. D., Rao, M. S., Blau, C. A., & Robins, A. J. (2007). Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling. Blood. https://doi.org/10.1182/blood-2007-03-082586

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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