Optogenetic BMP4 models symmetry breaking and primitive streak formation in hPSCs
- 1Cincinnati Children's Hospital Medical Center
Abstract
Gastrulation begins when the epiblast epithelium breaks symmetry to form the primitive streak, but current in vitro models neither fully capture this process nor separate its mechanical and chemical inputs. Here, we introduce LightBMP, an optogenetic platform that enables spatiotemporally programmable BMP4 expression in human pluripotent stem cells. Dose and duration control reveal a sustained low-BMP regime, inaccessible to recombinant ligand, that specifies mesoderm. Spatially programmed BMP4 sources in uniform cultures mimic the radial organization of 2D gastruloids, showing that mechan-ical context and edge sensing are not required for patterning. In micropatterned colo-nies, light-defined sources break symmetry to generate a stripe-shaped, primitive-streak-like domain where cells acquire multiple mesodermal fates and undergo directed migration. Together, these results show that spatial control of a single morphogen source is sufficient to drive symmetry breaking and primitive-streak-like patterning, independent of edge constraints.
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BibTeX
@misc{streletskaia2026optogenetic,
title = {{Optogenetic BMP4 models symmetry breaking and primitive streak formation in hPSCs}},
author = {A. Streletskaia and C. J. Bashor and A. Warmflash},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.755984},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.755984v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Optogenetic BMP4 models symmetry breaking and primitive streak formation in hPSCs
AU - A. Streletskaia
AU - C. J. Bashor
AU - A. Warmflash
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.755984
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.755984v1
AB - Gastrulation begins when the epiblast epithelium breaks symmetry to form the primitive streak, but current in vitro models neither fully capture this process nor separate its mechanical and chemical inputs. Here, we introduce LightBMP, an optogenetic platform that enables spatiotemporally programmable BMP4 expression in human pluripotent stem cells. Dose and duration control reveal a sustained low-BMP regime, inaccessible to recombinant ligand, that specifies mesoderm. Spatially programmed BMP4 sources in uniform cultures mimic the radial organization of 2D gastruloids, showing that mechan-ical context and edge sensing are not required for patterning. In micropatterned colo-nies, light-defined sources break symmetry to generate a stripe-shaped, primitive-streak-like domain where cells acquire multiple mesodermal fates and undergo directed migration. Together, these results show that spatial control of a single morphogen source is sufficient to drive symmetry breaking and primitive-streak-like patterning, independent of edge constraints.
ER -