한빛사
>
한빛사논문
한빛사논문
- 조회101
Cell Stem Cell, May 01, 2025 | https://doi.org/10.1016/j.stem.2025.04.006
Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines
Soraya Scuderi,1,2,8 Tae-Yun Kang,1,3,4,8 Alexandre Jourdon,1,2,8 Alex Nelson,1,2 Liang Yang,1,3,4 Feinan Wu,1,2 George M. Anderson,2 Jessica Mariani,1,2 Livia Tomasini,1,2 Vivekananda Sarangi,1,5 Alexej Abyzov,1,5 Andre Levchenko,1,3,4,* and Flora M. Vaccarino 1,2,6,7,9,*
1Program in Neurodevelopment and Regeneration, Yale University, New Haven, CT 06520, USA
2Child Study Center, Yale University, New Haven, CT 06520, USA
3Systems Biology Institute, Yale University, West Haven, CT 06516, USA
4Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
5Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
6Department of Neuroscience, Yale University, New Haven, CT 06520, USA
7Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA
8These authors contributed equally
9Lead contact
2Child Study Center, Yale University, New Haven, CT 06520, USA
3Systems Biology Institute, Yale University, West Haven, CT 06516, USA
4Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
5Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
6Department of Neuroscience, Yale University, New Haven, CT 06520, USA
7Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA
8These authors contributed equally
9Lead contact
*Corresponding authors: correspondence to Andre Levchenko or Flora M. Vaccarino
Abstract
The repertoire of neurons and their progenitors depends on their location along the antero-posterior and dorso-ventral axes of the neural tube. To model these axes, we designed the Dual Orthogonal-Morphogen Assisted Patterning System (Duo-MAPS) diffusion device to expose spheres of induced pluripotent stem cells (iPSCs) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison with single-cell transcriptomes from the fetal human brain revealed that Duo-MAPS-patterned organoids generated an extensive diversity of neuronal lineages from the forebrain, midbrain, and hindbrain. WNT and SHH crosstalk translated into early patterns of gene expression programs associated with the generation of specific brain lineages with distinct functional networks. Human iPSC lines showed substantial interindividual and line-to-line variations in their response to morphogens, highlighting that genetic and epigenetic variations may influence regional specification. Morphogen gradients promise to be a key approach to model the brain in its entirety.
논문정보
- Research article
- 2025년 05월 (BRIC 등록일 2025-05-07)
- 국외 연구진
- 생명과학 > 발생생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
