TY - JOUR
T1 - Neuroectoderm-derived iris muscle characterization at the single-cell resolution in native human iris and a pluripotent stem cell eye model
AU - Makovoz, Bar
AU - Eriksen, Anne Z.
AU - Warrington, Rachael E.
AU - Williams, Damian
AU - Blenkinsop, Timothy A.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - How the neuroectoderm-derived eye field breaks symmetry to specify iris muscle is not well understood. Recent studies have begun to transcriptionally characterize mouse iris muscle; however, little is known about the transcriptional foundation of human iris development. Human pluripotent stem cells (hPSCs) enable the study of iris muscle specification. Here we compare iris smooth muscle from native adult iris tissues to evaluate successful specification of iris muscle from hPSC lines. We utilize a previously published eye-like organoid protocol that specified cells of the eye field to also generate iris muscle. We describe a population transcriptionally similar to native iris and describe an iris muscle gene signature. Human iris muscle not only contains pigment, but also expresses pigment synthesis genes and is responsive to acetylcholine. Integration of single-cell RNA-seq datasets confirm the similarity between the iris muscle to the adult iris, establishing the usefulness of the model in studying neuroectoderm-derived iris muscle specification, and related diseases.
AB - How the neuroectoderm-derived eye field breaks symmetry to specify iris muscle is not well understood. Recent studies have begun to transcriptionally characterize mouse iris muscle; however, little is known about the transcriptional foundation of human iris development. Human pluripotent stem cells (hPSCs) enable the study of iris muscle specification. Here we compare iris smooth muscle from native adult iris tissues to evaluate successful specification of iris muscle from hPSC lines. We utilize a previously published eye-like organoid protocol that specified cells of the eye field to also generate iris muscle. We describe a population transcriptionally similar to native iris and describe an iris muscle gene signature. Human iris muscle not only contains pigment, but also expresses pigment synthesis genes and is responsive to acetylcholine. Integration of single-cell RNA-seq datasets confirm the similarity between the iris muscle to the adult iris, establishing the usefulness of the model in studying neuroectoderm-derived iris muscle specification, and related diseases.
UR - https://www.scopus.com/pages/publications/105023231783
U2 - 10.1038/s41467-025-65653-8
DO - 10.1038/s41467-025-65653-8
M3 - Article
C2 - 41309590
AN - SCOPUS:105023231783
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10648
ER -