%0 Journal Article
%T Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells.
%A Capdevila C
%A Miller J
%A Cheng L
%A Kornberg A
%A George JJ
%A Lee H
%A Botella T
%A Moon CS
%A Murray JW
%A Lam S
%A Calderon RI
%A Malagola E
%A Whelan G
%A Lin CS
%A Han A
%A Wang TC
%A Sims PA
%A Yan KS
%J Cell
%V 187
%N 12
%D 2024 Jun 6
%M 38848677
%F 66.85
%R 10.1016/j.cell.2024.05.001
%X In the prevailing model, Lgr5+ cells are the only intestinal stem cells (ISCs) that sustain homeostatic epithelial regeneration by upward migration of progeny through elusive upper crypt transit-amplifying (TA) intermediates. Here, we identify a proliferative upper crypt population marked by 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, is an essential factor for crypt proliferation and epithelial homeostasis. Our findings support a model in which tissue regeneration originates from upper crypt Fgfbp1+ cells that generate progeny propagating bi-directionally along the crypt-villus axis and serve as a source of Lgr5+ cells in the crypt base.