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A patterned human neural tube model using microfluidic gradients.
Xue, Xufeng; Kim, Yung Su; Ponce-Arias, Alfredo-Isaac; O'Laughlin, Richard; Yan, Robin Zhexuan; Kobayashi, Norio; Tshuva, Rami Yair; Tsai, Yu-Hwai; Sun, Shiyu; Zheng, Yi; Liu, Yue; Wong, Frederick C K; Surani, Azim; Spence, Jason R; Song, Hongjun; Ming, Guo-Li; Reiner, Orly; Fu, Jianping.
Afiliación
  • Xue X; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Kim YS; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Ponce-Arias AI; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
  • O'Laughlin R; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
  • Yan RZ; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
  • Kobayashi N; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Tshuva RY; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Tsai YH; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
  • Sun S; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
  • Zheng Y; Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Liu Y; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Wong FCK; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Surani A; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Spence JR; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
  • Song H; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
  • Ming GL; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
  • Reiner O; Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Fu J; Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
Nature ; 628(8007): 391-399, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38408487
ABSTRACT
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tipificación del Cuerpo / Microfluídica / Tubo Neural Límite: Humans Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tipificación del Cuerpo / Microfluídica / Tubo Neural Límite: Humans Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido