Rapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells

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dc.citation.articleNumbere40526en_US
dc.citation.journalTitleeLifeen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorHeemskerk, Idseen_US
dc.contributor.authorBurt, Karien_US
dc.contributor.authorMiller, Matthewen_US
dc.contributor.authorChhabra, Sapnaen_US
dc.contributor.authorGuerra, M.Ceciliaen_US
dc.contributor.authorLiu, Lizhongen_US
dc.contributor.authorWarmflash, Aryehen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgBiosciencesen_US
dc.date.accessioned2019-12-06T15:32:25Zen_US
dc.date.available2019-12-06T15:32:25Zen_US
dc.date.issued2019en_US
dc.description.abstractDuring embryonic development, diffusible signaling molecules called morphogens are thought to determine cell fates in a concentration-dependent way. Yet, in mammalian embryos, concentrations change rapidly compared to the time for making cell fate decisions. Here, we use human embryonic stem cells (hESCs) to address how changing morphogen levels influence differentiation, focusing on how BMP4 and Nodal signaling govern the cell-fate decisions associated with gastrulation. We show that BMP4 response is concentration dependent, but that expression of many Nodal targets depends on rate of concentration change. Moreover, in a self-organized stem cell model for human gastrulation, expression of these genes follows rapid changes in endogenous Nodal signaling. Our study shows a striking contrast between the specific ways ligand dynamics are interpreted by two closely related signaling pathways, highlighting both the subtlety and importance of morphogen dynamics for understanding mammalian embryogenesis and designing optimized protocols for directed stem cell differentiation.en_US
dc.identifier.citationHeemskerk, Idse, Burt, Kari, Miller, Matthew, et al.. "Rapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells." <i>eLife,</i> 8, (2019) eLife Sciences Publications, Ltd: https://doi.org/10.7554/eLife.40526.en_US
dc.identifier.digitalelife-40526en_US
dc.identifier.doihttps://doi.org/10.7554/eLife.40526en_US
dc.identifier.urihttps://hdl.handle.net/1911/107797en_US
dc.language.isoengen_US
dc.publishereLife Sciences Publications, Ltden_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleRapid changes in morphogen concentration control self-organized patterning in human embryonic stem cellsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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