Lineage marker synchrony in hematopoietic genealogies refutes the PU.1/GATA1 toggle switch paradigm

Nature Communications
Michael K StrasserCarsten Marr

Abstract

Molecular regulation of cell fate decisions underlies health and disease. To identify molecules that are active or regulated during a decision, and not before or after, the decision time point is crucial. However, cell fate markers are usually delayed and the time of decision therefore unknown. Fortunately, dividing cells induce temporal correlations in their progeny, which allow for retrospective inference of the decision time point. We present a computational method to infer decision time points from correlated marker signals in genealogies and apply it to differentiating hematopoietic stem cells. We find that myeloid lineage decisions happen generations before lineage marker onsets. Inferred decision time points are in agreement with data from colony assay experiments. The levels of the myeloid transcription factor PU.1 do not change during, but long after the predicted lineage decision event, indicating  that the PU.1/GATA1 toggle switch paradigm cannot explain the initiation of early myeloid lineage choice.

References

Jan 1, 1985·Journal of Molecular Evolution·M HasegawaT Yano
Jan 1, 1997·Annual Review of Public Health·E T Lee, O T Go
May 11, 2005·Nature Reviews. Genetics·Mads KaernJames J Collins
Apr 7, 2007·Developmental Biology·Sui HuangTariq Enver
Sep 7, 2007·PLoS Biology·Benjamin B KaufmannAlexander van Oudenaarden
Feb 26, 2008·Cell·Stuart H Orkin, Leonard I Zon
Feb 3, 2009·Mathematical Medicine and Biology : a Journal of the IMA·Pavol BokesMatthew Loose
Jul 11, 2009·Science·Michael A RiegerTimm Schroeder
Jul 25, 2009·Bioinformatics·Victor OlariuVisakan Kadirkamanathan
Jul 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·E D HawkinsP D Hodgkin
Dec 4, 2009·Nature·Thomas Graf, Tariq Enver
Apr 5, 2011·Journal of Mathematical Biology·Campbell DuffTianhai Tian
Sep 3, 2011·Nature Reviews. Molecular Cell Biology·Leo D Wang, Amy J Wagers
Feb 4, 2012·PLoS Biology·Joe H LevineMichael B Elowitz
Mar 24, 2012·Cancer Cell·Jeffrey A MageeSean J Morrison
Mar 30, 2012·Nature Reviews. Genetics·Ziheng Yang, Bruce Rannala
Jun 20, 2012·The FEBS Journal·Carsten MarrFabian J Theis
Feb 15, 2013·Nature·Björn SchwanhäusserMatthias Selbach
Aug 15, 2013·Journal of Cell Science·Daniel L Coutu, Timm Schroeder
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Rob MorrisJuan Carlos Izpisua Belmonte
Dec 18, 2014·Cell Stem Cell·Martin EtzrodtTimm Schroeder
Feb 2, 2015·Bioinformatics·Theresa NiederbergerAchim Tresch
Sep 22, 2015·Nature Cell Biology·Adam FilipczykTimm Schroeder
Sep 24, 2015·BMC Systems Biology·Michael K StrasserCarsten Marr
Nov 23, 2015·The Journal of Chemical Physics·Davit A Potoyan, Peter G Wolynes
Jul 13, 2016·Nature Biotechnology·Oliver HilsenbeckTimm Schroeder
Nov 9, 2016·Nature Biotechnology·Stavroula SkylakiTimm Schroeder
Mar 21, 2017·Nature Cell Biology·Lars VeltenLars M Steinmetz
Dec 7, 2017·Journal of Theoretical Biology·Tanja StadlerTimm Schroeder
Dec 26, 2017·Current Opinion in Cell Biology·Martin Etzrodt, Timm Schroeder

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Citations

Feb 13, 2019·PLoS Computational Biology·Damien G HicksSarah M Russell
Feb 8, 2019·Blood·Dirk Loeffler, Timm Schroeder
Dec 10, 2019·Annals of the New York Academy of Sciences·Dirk LoefflerTimm Schroeder
Dec 19, 2018·Nature Communications·Shaon ChakrabartiFranziska Michor
Jul 6, 2019·Frontiers in Cell and Developmental Biology·Geoffrey Brown, Rhodri Ceredig
Jun 26, 2020·Nature·Justin C WheatUlrich Steidl
Oct 27, 2020·Computational and Structural Biotechnology Journal·Anne L PlantJeffrey Stinson
Jan 16, 2021·Science·T StadlerM P H Stumpf
Jun 16, 2021·The Journal of Experimental Medicine·Tobias Kull, Timm Schroeder
Nov 25, 2021·The Journal of Experimental Medicine·Nouraiz AhmedTimm Schroeder

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