TY - JOUR
KW - Biomedical Engineering
KW - Embryogenesis
KW - Neural patterning
KW - Pluripotent Stem Cells
AU - Xufeng Xue
AU - Yung Su Kim
AU - Alfredo-Isaac Ponce-Arias
AU - Richard O’Laughlin
AU - Robin Zhexuan Yan
AU - Norio Kobayashi
AU - Rami Yair Tshuva
AU - Yu-Hwai Tsai
AU - Shiyu Sun
AU - Yi Zheng
AU - Yue Liu
AU - Frederick C. K. Wong
AU - Azim Surani
AU - Jason R. Spence
AU - Hongjun Song
AU - Guo-li Ming
AU - Orly Reiner
AU - Jianping Fu
AB - The human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural tube, the embryonic precursor to the human nervous system. Historically, studies of neural tube patterning have relied on animal models to uncover underlying principles. Recently, models of neurodevelopment based on human pluripotent stem cells, including neural organoids1–5 and bioengineered neural tube development models6–10, have emerged. However, such models fail to recapitulate neural patterning along both rostral–caudal and dorsal–ventral axes in a three-dimensional tubular geometry, a hallmark of neural tube development. Here we report a human pluripotent stem cell-based, microfluidic neural tube-like structure, the development of which recapitulates several crucial aspects of neural patterning in brain and spinal cord regions and along rostral–caudal and dorsal–ventral axes. This structure was utilized for studying neuronal lineage development, which revealed pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and the caudal gene CDX2 in spinal cord and trunk neural crest development. We further developed dorsal–ventral patterned microfluidic forebrain-like structures with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic development of the human forebrain pallium and subpallium, respectively. Together, these microfluidics-based neurodevelopment models provide three-dimensional lumenal tissue architectures with in vivo-like spatiotemporal cell differentiation and organization, which will facilitate the study of human neurodevelopment and disease.
BT - Nature
DA - 2024-02-26
DO - 10.1038/s41586-024-07204-7
LA - en
N2 - The human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural tube, the embryonic precursor to the human nervous system. Historically, studies of neural tube patterning have relied on animal models to uncover underlying principles. Recently, models of neurodevelopment based on human pluripotent stem cells, including neural organoids1–5 and bioengineered neural tube development models6–10, have emerged. However, such models fail to recapitulate neural patterning along both rostral–caudal and dorsal–ventral axes in a three-dimensional tubular geometry, a hallmark of neural tube development. Here we report a human pluripotent stem cell-based, microfluidic neural tube-like structure, the development of which recapitulates several crucial aspects of neural patterning in brain and spinal cord regions and along rostral–caudal and dorsal–ventral axes. This structure was utilized for studying neuronal lineage development, which revealed pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and the caudal gene CDX2 in spinal cord and trunk neural crest development. We further developed dorsal–ventral patterned microfluidic forebrain-like structures with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic development of the human forebrain pallium and subpallium, respectively. Together, these microfluidics-based neurodevelopment models provide three-dimensional lumenal tissue architectures with in vivo-like spatiotemporal cell differentiation and organization, which will facilitate the study of human neurodevelopment and disease.
PY - 2024
SP - 391
EP - 399
T2 - Nature
TI - A patterned human neural tube model using microfluidic gradients
UR - https://www.nature.com/articles/s41586-024-07204-7
VL - 628
Y2 - 2024-08-13
SN - 1476-4687
ER -