Dundes Carolyn E, Jokhai Rayyan T, Ahsan Hadia, Kang Rachel S, Salomon-Shulman Rachel E A, Rajan Arjun, Kim Yoon Seok, Stanton Liam J, Xu Christine, Do Stephanie, McDonald Brennan D, López José Miguel Andrade, Urrutia Hugo A, Greenfeld Hannah, Wong Alicia, Qu Yimiao, Petkovic Andrew S, Miao Yi, Garcia K Christopher, Monje Michelle, Wagner Daniel E, Bronner Marianne E, Lowe Christopher J, Loh Kyle M
Department of Developmental Biology, Stanford University, Stanford, CA USA.
Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA USA.
bioRxiv. 2025 Jul 5:2025.07.02.662771. doi: 10.1101/2025.07.02.662771.
The hindbrain is a life-sustaining brain region. In one model, a common neural progenitor generates all brain regions. Here our studies of mouse embryos and human pluripotent stem cells (hPSCs) support a different model: two parallel brain progenitors emerge simultaneously during gastrulation, anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor). Not only are they lineage-committed to respectively form forebrain/midbrain vs. hindbrain , but they also have diverging chromatin landscapes foreshadowing future forebrain/midbrain vs. hindbrain identities. Leveraging these differences, we differentiated hPSCs into hindbrain rhombomere 5/6-specific motor neurons, hitherto difficult to generate . We postulate the brain is a composite organ emanating from two lineage-restricted progenitors; these dual progenitors may be evolutionarily conserved across 550 million years from hemichordates to mammals.
后脑是维持生命的脑区。在一种模型中，一种共同的神经祖细胞生成所有脑区。在这里，我们对小鼠胚胎和人类多能干细胞（hPSC）的研究支持了另一种模型：在原肠胚形成过程中，两种平行的脑祖细胞同时出现，即前神经外胚层（前脑/中脑祖细胞）和后神经外胚层（后脑祖细胞）。它们不仅分别定向分化形成前脑/中脑与后脑，而且还具有不同的染色质景观，预示着未来前脑/中脑与后脑的特征。利用这些差异，我们将hPSC分化为后脑菱脑节5/6特异性运动神经元，这在此前很难实现。我们推测，脑是一个由两个谱系受限的祖细胞产生的复合器官；从半索动物到哺乳动物，这两种双祖细胞可能在5.5亿年的进化过程中一直保守存在。
