Hsin Jenny, Yazejian Rita M, Pajanoja Ceren, Kerosuo Laura
National Institute of Dental and Craniofacial Research, Intramural Research Program, Neural Crest Development and Disease Unit, National Institutes of Health, Bethesda, MD, USA; Biointerface Group, Department of Engineering, University of Cambridge, Cambridge, UK; UAB Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA.
National Institute of Dental and Craniofacial Research, Intramural Research Program, Neural Crest Development and Disease Unit, National Institutes of Health, Bethesda, MD, USA.
Differentiation. 2025 Jul-Aug;144:100866. doi: 10.1016/j.diff.2025.100866. Epub 2025 May 15.
The neural crest (NC) is a transient population of pluripotent-like, pleistopotent stem cells that emerges early in vertebrate development. These cells play a pivotal role in generating a diverse array of tissues, including the craniofacial bone and cartilage, the entire peripheral nervous system, melanocytes of the skin, certain cardiac structures, and chromaffin cells of the adrenal medulla, among others. The stem cell potential of neural crest cells (NCCs) has long intrigued developmental biologists, as the NC originates post-gastrulation in the ectoderm, yet NCCs also give rise to derivatives typically associated with mesodermal or endodermal origins. Recent work has shown that NCCs co-express factors known from the core pluripotency complex from the pre-gastrulation stages in the epiblast, which enables their exceptionally high stem cell potential. However, detailed spatiotemporal data on pluripotency factor expression in vertebrate embryos remain limited, and the distinction between the function of co-expression of pluripotency genes versus their individual expression in the developing embryo is not clear. In this study, to elucidate the NCC formation process across axial levels as well as the putative different roles of these stem cell genes during early embryogenesis, we used multi-channel fluorescent in situ hybridization to comprehensively examine the anterior-to-posterior expression of pluripotency factors PouV (Oct4), Nanog, Klf4 and Lin28A in chick embryos across key developmental stages, from Hamburger and Hamilton (HH) stage 5 to stage 14. From head to trunk, we find that while the early ectoderm, including the future epidermis and central nervous system (CNS) domains, in the neural fold stages broadly co-express these genes, their expression profiles differ significantly after neurulation. Nanog expression remains in the hindbrain and vagal migratory NCCs. Klf4 strongly marks the developing floor plate, and Klf4, PouV and Lin28A are expressed also in the neural tube that forms the CNS as well as in the developing somites, implying additional roles for these factors during embryogenesis.
神经嵴(NC)是一群多能样、多能干细胞,在脊椎动物发育早期出现。这些细胞在生成多种组织中起关键作用,包括颅面骨和软骨、整个外周神经系统、皮肤黑素细胞、某些心脏结构以及肾上腺髓质的嗜铬细胞等。神经嵴细胞(NCCs)的干细胞潜能长期以来一直吸引着发育生物学家,因为神经嵴在原肠胚形成后起源于外胚层,但NCCs也会产生通常与中胚层或内胚层起源相关的衍生物。最近的研究表明,NCCs共同表达来自上胚层原肠胚形成前阶段核心多能性复合体的因子,这赋予了它们极高的干细胞潜能。然而,关于脊椎动物胚胎中多能性因子表达的详细时空数据仍然有限,并且在发育胚胎中多能性基因共同表达的功能与其单独表达的功能之间的区别尚不清楚。在本研究中,为了阐明跨轴向水平的NCC形成过程以及这些干细胞基因在早期胚胎发生过程中可能的不同作用,我们使用多通道荧光原位杂交技术,全面检测了从哈伯格和汉密尔顿(HH)第5阶段到第14阶段的鸡胚中多能性因子PouV(Oct4)、Nanog、Klf4和Lin28A从前到后的表达情况。从头至躯干,我们发现,虽然在神经褶阶段,包括未来表皮和中枢神经系统(CNS)区域的早期外胚层广泛共同表达这些基因,但在神经胚形成后它们的表达谱有显著差异。Nanog表达保留在后脑和迷走迁移的NCCs中。Klf4强烈标记发育中的底板,并且Klf4、PouV和Lin28A也在形成CNS的神经管以及发育中的体节中表达,这意味着这些因子在胚胎发生过程中还有其他作用。