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Hematopoiesis and T-cell specification as a model developmental system

Rothenberg, Ellen V. and Kueh, Hao Yuan and Yui, Mary A. and Zhang, Jingli A. (2016) Hematopoiesis and T-cell specification as a model developmental system. Immunological Reviews, 271 (1). pp. 72-97. ISSN 0105-2896. PMCID PMC4837658.

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The pathway to generate T cells from hematopoietic stem cells guides progenitors through a succession of fate choices while balancing differentiation progression against proliferation, stage to stage. Many elements of the regulatory system that controls this process are known, but the requirement for multiple, functionally distinct transcription factors needs clarification in terms of gene network architecture. Here, we compare the features of the T-cell specification system with the rule sets underlying two other influential types of gene network models: first, the combinatorial, hierarchical regulatory systems that generate the orderly, synchronized increases in complexity in most invertebrate embryos; second, the dueling ‘master regulator’ systems that are commonly used to explain bistability in microbial systems and in many fate choices in terminal differentiation. The T-cell specification process shares certain features with each of these prevalent models but differs from both of them in central respects. The T-cell system is highly combinatorial but also highly dose-sensitive in its use of crucial regulatory factors. The roles of these factors are not always T-lineage-specific, but they balance and modulate each other's activities long before any mutually exclusive silencing occurs. T-cell specification may provide a new hybrid model for gene networks in vertebrate developmental systems.

Item Type:Article
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URLURL TypeDescription CentralArticle
Rothenberg, Ellen V.0000-0002-3901-347X
Kueh, Hao Yuan0000-0001-6272-6673
Yui, Mary A.0000-0002-3136-2181
Additional Information:© 2016 John Wiley & Sons. Article first published online: 18 APR 2016. We gratefully acknowledge the late Eric Davidson for stimulating discussions of developmental gene network properties in diverse systems. We thank past and present members of the Rothenberg and Michael Elowitz groups for valuable advice and sharing of unpublished results, Maria Lerica Gutierrez Quiloan for mouse colony supervision, and Rochelle Diamond, Keith Beadle, and Diana Perez for flow cytometry. The ideas presented here were developed with support by grants from NIH: RC2CA148278, R01AI083514, R01AI095943, R01CA90233, R01HD076915 and R01HL119102 to E. V. R., R01AI064590 to M. A. Y., and K99HL119638A to H. Y. K.; also by the L. A. Garfinkle Memorial Laboratory Fund, and by the Albert Billings Ruddock Professorship to E. V. R. None of the authors has a conflict of interest.
Funding AgencyGrant Number
Louis A. Garfinkle Memorial Laboratory FundUNSPECIFIED
Albert Billings Ruddock ProfessorshipUNSPECIFIED
Subject Keywords:gene regulatory networks, transcription factors, commitment, lineage hierarchy
Issue or Number:1
PubMed Central ID:PMC4837658
Record Number:CaltechAUTHORS:20160425-152503200
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Official Citation:Rothenberg, E. V., Kueh, H. Y., Yui, M. A. and Zhang, J. A. (2016), Hematopoiesis and T-cell specification as a model developmental system. Immunological Reviews, 271: 72–97. doi: 10.1111/imr.12417
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66465
Deposited By: Tony Diaz
Deposited On:26 Apr 2016 02:20
Last Modified:09 Mar 2020 13:18

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