Person: Jadhav, Unmesh
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Publication Natural Selection, Crypt Fitness, and Pol III Dependency in the Intestine
(Elsevier, 2016) Jadhav, Unmesh; Shivdasani, RameshPublication Single-Cell Transcript Profiles Reveal Multilineage Priming in Early Progenitors Derived from Lgr5 + Intestinal Stem Cells
(Elsevier BV, 2016-08) Kim, Tae-Hee; Saadatpour, Assieh; Guo, Guoji; Saxena, Madhurima; Cavazza, Alessia; Desai, Niyati; Jadhav, Unmesh; Jiang, Lan; Rivera, Miguel; Orkin, Stuart; Yuan, Guo-Cheng; Shivdasani, RameshLgr5+ intestinal stem cells (ISC) 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.