التفاصيل البيبلوغرافية
| العنوان: |
Human neural tube morphogenesis in vitro by geometric constraints |
| المؤلفون: |
Karzbrun, Eyal, Khankhel, Aimal H, Megale, Heitor C, Glasauer, Stella MK, Wyle, Yofiel, Britton, George, Warmflash, Aryeh, Kosik, Kenneth S, Siggia, Eric D, Shraiman, Boris I, Streichan, Sebastian J |
| المصدر: |
Nature, vol 599, iss 7884 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2021 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biological Sciences, Engineering, Biomedical Engineering, Regenerative Medicine, Stem Cell Research - Embryonic - Human, Stem Cell Research, Pediatric, Stem Cell Research - Nonembryonic - Human, Neurosciences, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Ectoderm, Humans, Models, Biological, Morphogenesis, Neural Plate, Neural Tube, Neural Tube Defects, Organ Culture Techniques, Regeneration, Stem Cells, General Science & Technology |
| جغرافية الموضوع: |
268 - 272 |
| الوصف: |
Understanding human organ formation is a scientific challenge with far-reaching medical implications1,2. Three-dimensional stem-cell cultures have provided insights into human cell differentiation3,4. However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction5,6, neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior-posterior axis depends on neural ectoderm geometry in addition to molecular gradients7. Our approach provides anew route to the study of human organ morphogenesis in health and disease. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt8fg4s73w; https://escholarship.org/uc/item/8fg4s73wTest |
| الإتاحة: |
https://escholarship.org/uc/item/8fg4s73wTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.BF4C0B98 |
| قاعدة البيانات: |
BASE |
