McNeely Katrina C, Dwyer Noelle D
Department of Cell Biology, University of Virginia School of Medicine, PO Box 800732, Charlottesville, VA, USA.
Curr Stem Cell Rep. 2021 Dec;7(4):161-173. doi: 10.1007/s40778-021-00193-7. Epub 2021 Aug 11.
How stem cells balance proliferation with differentiation, giving rise to specific daughter cells during development to build an embryo or tissue, remains an open question. Here, we discuss recent evidence that cytokinetic abscission regulation in stem cells, particularly neural stem cells (NSCs), is part of the answer. Abscission is a multi-step process mediated by the midbody, a microtubule-based structure formed in the intercellular bridge between daughter cells after mitosis.
Human mutations and mouse knockouts in abscission genes reveal that subtle disruptions of NSC abscission can cause brain malformations. Experiments in several epithelial systems have shown that midbodies serve as scaffolds for apical junction proteins and are positioned near apical membrane fate determinants. Abscission timing is tightly controlled and developmentally regulated in stem cells, with delayed abscission in early embryos and faster abscission later. Midbody remnants (MBRs) contain over 400 proteins and may influence polarity, fate, and ciliogenesis.
As NSCs and other stem cells build tissues, they tightly regulate three aspects of abscission: midbody positioning, duration, and MBR handling. Midbody positioning and remnants establish or maintain cell polarity. MBRs are deposited on the apical membranes of epithelia, can be released or internalized by surrounding cells, and may sequester fate determinants or transfer information between cells. Work in cell lines and simpler systems has shown multiple roles for abscission regulation influencing stem cell polarity, potency, and daughter fates during development. Elucidating how the abscission process influences cell fate and tissue growth is important for our continued understanding of brain development and stem cell biology.
干细胞如何在增殖与分化之间取得平衡，从而在发育过程中产生特定的子代细胞以构建胚胎或组织，这仍然是一个悬而未决的问题。在此，我们讨论近期的证据，即干细胞尤其是神经干细胞（NSC）中的胞质分裂切割调控是答案的一部分。切割是一个由中间体介导的多步骤过程，中间体是有丝分裂后在子代细胞之间的细胞间桥中形成的基于微管的结构。
切割基因中的人类突变和小鼠基因敲除表明，NSC切割的细微破坏会导致脑畸形。在多个上皮系统中的实验表明，中间体作为顶端连接蛋白的支架，并定位在顶端膜命运决定因素附近。干细胞中的切割时间受到严格控制且具有发育调控性，早期胚胎中的切割延迟，后期则更快。中间体残余物（MBR）包含400多种蛋白质，可能会影响极性、命运和纤毛发生。
当NSC和其他干细胞构建组织时，它们会严格调控切割的三个方面：中间体定位、持续时间和MBR处理。中间体定位和残余物建立或维持细胞极性。MBR沉积在上皮细胞的顶端膜上，可以被周围细胞释放或内化，并可能隔离命运决定因素或在细胞间传递信息。细胞系和更简单系统中的研究表明，切割调控在发育过程中对干细胞极性、潜能和子代命运具有多种作用。阐明切割过程如何影响细胞命运和组织生长对于我们持续理解脑发育和干细胞生物学很重要。
