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造血微环境通过受邻近组织和Slit-Robo信号传导控制的集体细胞迁移而形成。

The hematopoietic niche assembles through collective cell migration controlled by neighbor tissues and Slit-Robo signaling.

作者信息

Nelson Kara A, Lenhart Kari F, Anllo Lauren, DiNardo Stephen

机构信息

Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States.

Institute for Regenerative Medicine at the University of Pennsylvania, Philadelphia, United States.

出版信息

Elife. 2025 Jan 3;13:RP100455. doi: 10.7554/eLife.100455.

Abstract

Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established. To address this, we investigated the formation of a genetically tractable niche, the Posterior Signaling Center (PSC), the assembly of which had not been previously explored. This niche controls hematopoietic progenitors of the lymph gland (LG). PSC cells were previously shown to be specified laterally in the embryo, but ultimately reside dorsally, at the LG posterior. Here, using live-imaging, we show that PSC cells migrate as a tight collective and associate with multiple tissues during their trajectory to the LG posterior. We find that Slit emanating from two extrinsic sources, visceral mesoderm and cardioblasts, is required for the PSC to remain a collective, and for its attachment to cardioblasts during migration. Without proper Slit-Robo signaling, PSC cells disperse, form aberrant contacts, and ultimately fail to reach their stereotypical position near progenitors. Our work characterizes a novel example of niche formation and identifies an extrinsic signaling relay that controls precise niche positioning.

摘要

小生境通常在组织中相对于其所支持的干细胞的特定位置被发现。小生境位置的一致性表明其位置对于小生境功能很重要。然而,大多数小生境的复杂性使得人们无法彻底了解它们是如何确定其正确位置的。为了解决这个问题,我们研究了一个具有遗传易处理性的小生境——后部信号中心(PSC)的形成,其组装过程此前尚未被探索过。这个小生境控制着淋巴腺(LG)的造血祖细胞。先前的研究表明,PSC细胞在胚胎中是从侧面特化而来的,但最终位于LG后部的背侧。在这里,我们通过实时成像显示,PSC细胞作为一个紧密的细胞群迁移,并在其迁移到LG后部的轨迹中与多种组织相互作用。我们发现,来自内脏中胚层和成心肌细胞这两个外部来源的Slit对于PSC保持细胞群状态以及在迁移过程中附着于成心肌细胞是必需的。如果没有适当的Slit-Robo信号传导,PSC细胞就会分散,形成异常的接触,最终无法到达其在祖细胞附近的固定位置。我们的工作描述了小生境形成的一个新例子,并确定了一个控制小生境精确定位的外部信号传导途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5af/11698496/2bdad550652a/elife-100455-fig1.jpg

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