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

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dc.citation.articleNumbere40526
dc.citation.journalTitleeLife
dc.citation.volumeNumber8
dc.contributor.authorHeemskerk, Idse
dc.contributor.authorBurt, Kari
dc.contributor.authorMiller, Matthew
dc.contributor.authorChhabra, Sapna
dc.contributor.authorGuerra, M.Cecilia
dc.contributor.authorLiu, Lizhong
dc.contributor.authorWarmflash, Aryeh
dc.date.accessioned2019-12-06T15:32:25Z
dc.date.available2019-12-06T15:32:25Z
dc.date.issued2019
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.
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.
dc.identifier.digitalelife-40526
dc.identifier.doihttps://doi.org/10.7554/eLife.40526
dc.identifier.urihttps://hdl.handle.net/1911/107797
dc.language.isoeng
dc.publishereLife Sciences Publications, Ltd
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleRapid changes in morphogen concentration control self-organized patterning in human embryonic stem cells
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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