The adult intestinal stem cells (ISCs) are transcriptionally heterogeneous. As the mechanisms governing their developmental specification are still poorly understood, whether this heterogeneity reflects an early determination of distinct cellular sub-types with potentially distinct physiological functions remains an open question. We investigate the cellular heterogeneity within the mouse embryonic midgut epithelium at the molecular and functional levels. Cell fate mapping analysis revealed that multiple early embryonic epithelial progenitors give rise to Lgr5 ISCs. The origin of the molecularly distinct early precursors along the anterior-posterior axis defines the transcriptional signature of embryonic Lgr5 ISC progenitors. We further show that the early epithelial progenitors have different capacity to generate Lgr5 ISC progenitors and Axin2 early precursors display the highest potential.

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http://dx.doi.org/10.1016/j.ydbio.2017.10.012DOI Listing

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