First Author | Kim TH | Year | 2016 |
Journal | Cell Rep | Volume | 16 |
Issue | 8 | Pages | 2053-2060 |
PubMed ID | 27524622 | Mgi Jnum | J:238942 |
Mgi Id | MGI:5824610 | Doi | 10.1016/j.celrep.2016.07.056 |
Citation | Kim TH, et al. (2016) Single-Cell Transcript Profiles Reveal Multilineage Priming in Early Progenitors Derived from Lgr5(+) Intestinal Stem Cells. Cell Rep 16(8):2053-60 |
abstractText | Lgr5(+) intestinal stem cells (ISCs) drive epithelial self-renewal, and their immediate progeny-intestinal bipotential progenitors-produce absorptive and secretory lineages via lateral inhibition. To define features of early transit from the ISC compartment, we used a microfluidics approach to measure selected stem- and lineage-specific transcripts in single Lgr5(+) cells. We identified two distinct cell populations, one that expresses known ISC markers and a second, abundant population that simultaneously expresses markers of stem and mature absorptive and secretory cells. Single-molecule mRNA in situ hybridization and immunofluorescence verified expression of lineage-restricted genes in a subset of Lgr5(+) cells in vivo. Transcriptional network analysis revealed that one group of Lgr5(+) cells arises from the other and displays characteristics expected of bipotential progenitors, including activation of Notch ligand and cell-cycle-inhibitor genes. These findings define the earliest steps in ISC differentiation and reveal multilineage gene priming as a fundamental property of the process. |