美国哥伦比亚大学Kelley S. Yan小组发现，时间分辨命运图谱确定肠上隐窝区是Lgr5+隐窝基底柱状细胞的起源地。2024年6月6日，国际知名学术期刊《细胞》发表了这一成果。
研究人员在推定的过渡-扩增（TA）细胞位置发现了以Fgfbp1为标志的增殖性上隐窝群体，它在转录上有别于Lgr5+细胞。利用动力学报告器进行时间分辨命运图谱绘制和Fgfbp1-CreERT2谱系追踪，研究人员确定Fgfbp1+细胞具有多种潜能并能产生Lgr5+细胞，这与其ISC功能一致。Fgfbp1+细胞还能在Lgr5+细胞耗竭后维持上皮再生。
研究人员证明了由上隐窝细胞产生的FGFBP1是隐窝增殖和上皮稳态的重要因子。研究结果支持这样一种模型，即组织再生源于隐窝上部的Fgfbp1+细胞，它们产生的后代沿隐窝-绒毛双向传播，并成为隐窝底部Lgr5+细胞的来源。
据了解，在流行的模型中，Lgr5+细胞是唯一的肠干细胞（ISC），它们通过难以捉摸的上隐窝TA中间体向上迁移后代，维持稳态上皮再生。
附：英文原文
Title: Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells
Author: Claudia Capdevila, Jonathan Miller, Liang Cheng, Adam Kornberg, Joel J. George, Hyeonjeong Lee, Theo Botella, Christine S. Moon, John W. Murray, Stephanie Lam, Ruben I. Calderon, Ermanno Malagola, Gary Whelan, Chyuan-Sheng Lin, Arnold Han, Timothy C. Wang, Peter A. Sims, Kelley S. Yan
Issue&Volume: 2024/06/06
Abstract: In the prevailing model, Lgr5+ cells are the only intestinal stem cells (ISCs) that sustain homeostatic epithelialregeneration by upward migration of progeny through elusive upper crypt transit-amplifying(TA) intermediates. Here, we identify a proliferative upper crypt population markedby Fgfbp1, in the location of putative TA cells, that is transcriptionally distinct from Lgr5+ cells. Using a kinetic reporter for time-resolved fate mapping and Fgfbp1-CreERT2 lineage tracing, we establish that Fgfbp1+ cells are multi-potent and give rise to Lgr5+ cells, consistent with their ISC function. Fgfbp1+ cells also sustain epithelial regeneration following Lgr5+ cell depletion. We demonstrate that FGFBP1, produced by the upper crypt cells, isan essential factor for crypt proliferation and epithelial homeostasis. Our findingssupport a model in which tissue regeneration originates from upper crypt Fgfbp1+ cells that generate progeny propagating bi-directionally along the crypt-villusaxis and serve as a source of Lgr5+ cells in the crypt base.
DOI: 10.1016/j.cell.2024.05.001
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00491-4