Settles Skylar E, Miller Kathleen E, Roberts-Galbraith Rachel H
Department of Genetics, University of Georgia.
Department of Cellular Biology, University of Georgia.
bioRxiv. 2025 Aug 2:2025.08.01.668211. doi: 10.1101/2025.08.01.668211.
Harnessing the extraordinary potential of stem cells requires exquisite control , , and in the context of potential therapies. Adult stem cells are commonly housed within a microenvironment, or "niche," that supplies signals to regulate stem cell function. It has been difficult to determine whether pluripotent stem cells have a similar endogenous niche due to the transient nature of the cell type in most animal species. We sought to establish the nature of a pluripotent stem cell niche using planarian flatworms, animals that maintain pluripotent stem cells throughout adulthood and use them for whole-body regeneration. We characterized the cellular microenvironment of planarian stem cells in detail, finding that each stem cell is surrounded by a diverse mixture of other stem cells and differentiated cells. We identified phagocytic cells marked by as the differentiated cell type most frequently found next to stem cells, in both homeostasis and regeneration. cells, which we named abraçada cells, wrap around stem cells, and then neighbor progenitors less often coincident with their specialization. We then tested whether abraçada cells constitute a functional niche that regulates stem cells. We identified two innexin-encoding genes expressed in abraçada cells that are critical for pluripotent stem cell function and planarian regeneration. Together, our results reveal for the first time a local, endogenous niche that actively regulates adult pluripotent stem cells.
利用干细胞的非凡潜能需要精确的控制，且在潜在治疗的背景下亦是如此。成体干细胞通常存在于一个微环境或“龛”中，该微环境提供信号来调节干细胞功能。由于在大多数动物物种中，多能干细胞类型具有短暂性，因此很难确定它们是否具有类似的内源性龛。我们试图利用涡虫来确定多能干细胞龛的性质，涡虫这种动物在成年期一直保持多能干细胞，并利用它们进行全身再生。我们详细描述了涡虫干细胞的细胞微环境，发现每个干细胞都被其他干细胞和分化细胞的多种混合物所包围。我们将标记为 的吞噬细胞确定为在稳态和再生过程中最常在干细胞旁边发现的分化细胞类型。 细胞，我们将其命名为abraçada细胞，环绕在干细胞周围，然后较少与祖细胞相邻，这与其特化情况相符。然后，我们测试了abraçada细胞是否构成调节干细胞的功能性龛。我们在abraçada细胞中鉴定出两个编码连接蛋白的基因，它们对多能干细胞功能和涡虫再生至关重要。总之，我们的结果首次揭示了一个积极调节成体多能干细胞的局部内源性龛。
