Person: McMahon, Jill Ann
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McMahon
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Jill Ann
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McMahon, Jill Ann
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Publication Neuroepithelial Body Microenvironment Is a Niche for a Distinct Subset of Clara-Like Precursors in the Developing Airways(Proceedings of the National Academy of Sciences, 2012) Guha, Arjun; Vasconcelos, Michelle; Cai, Yan; Yoneda, Mitsuhiro; Hinds, Anne; Qian, Jun; Li, Guihua; Dickel, Lauren; Johnson, Jane E.; Kimura, Shioko; Guo, Jinjin; McMahon, Jill Ann; McMahon, Andrew P.; Cardoso, Wellington V.Clara cells of mammalian airways have multiple functions and are morphologically heterogeneous. Although Notch signaling is essential for the development of these cells, it is unclear how Notch influences Clara cell specification and if diversity is established among Clara cell precursors. Here we identify expression of the secretoglobin Scgb3a2 and Notch activation as early events in a program of secretory cell fate determination in developing murine airways. We show that Scgb3a2 expression in vivo is Notch-dependent at early stages and ectopically induced by constitutive Notch1 activation, and also that in vitro Notch signaling together with the pan-airway transcription factor Ttf1 (Nkx2.1) synergistically regulate secretoglobin gene transcription. Furthermore, we identified a subpopulation of secretory precursors juxtaposed to presumptive neuroepithelial bodies (NEBs), distinguished by their strong Scgb3a2 and uroplakin 3a (Upk3a) signals and reduced Ccsp (Scgb1a1) expression. Genetic ablation of Ascl1 prevented NEB formation and selectively interfered with the formation of this subpopulation of cells. Lineage labeling of Upk3a-expressing cells during development showed that these cells remain largely uncommitted during embryonic development and contribute to Clara and ciliated cells in the adult lung. Together, our findings suggest a role for Notch in the induction of a Clara cell-specific program of gene expression, and reveals that the NEB microenvironment in the developing airways is a niche for a distinct subset of Clara-like precursors.Publication The Redshift Evolution of the Mean Temperature, Pressure, and Entropy Profiles in 80 SPT-Selected Galaxy Clusters(IOP Publishing, 2014) McDonald, M.; Benson, B. A.; Viklinin, Alexey; Aird, K. A.; Allen, S. W.; Bautz, Marshall William; Bayliss, Matthew; Bleem, L. E.; Bocquet, S.; Brodwin, M.; Carlstrom, J. E.; Chang, C. L.; Cho, Justina; Clocchiatti, A.; Crawford, T. M.; Crites, A. T.; de Haan, T.; Dobbs, M. A.; Foley, R. J.; Forman, William; George, E. M.; Gladders, M. D.; Gonzalez, A. H.; Halverson, N. W.; Hlavacek-Larrondo, J.; Holder, G. P.; Holzapfel, W. L.; Hrubes, J. D.; Jones, Christine; Keisler, R.; Knox, L.; Lee, A. T.; Leitch, E. M.; Liu, J.; Lueker, M.; Luong-Van, D.; Mantz, A.; Marrone, D. P.; McMahon, Jill Ann; Meyer, S. S.; Miller, Eric; Mocanu, L.; Mohr, J. J.; Murray, S. S.; Padin, S.; Pryke, C.; Reichardt, C. L.; Rest, Armin; Ruhl, J. E.; Saliwanchik, B. R.; Saro, A.; Sayre, James Edward; Schaffer, K. K.; Shirokoff, E.; Spieler, H. G.; Stalder, Brian; Stanford, S. A.; Staniszewski, Z.; Stark, Aaron William; Story, K. T.; Stubbs, Christopher; Vanderlinde, K.; Vieira, J. D.; Williamson, R.; Zahn, O.; Zenteno, A.We present the results of an X-ray analysis of 80 galaxy clusters selected in the 2500 deg2 South Pole Telescope survey and observed with the Chandra X-ray Observatory. We divide the full sample into subsamples of ∼20 clusters based on redshift and central density, performing a joint X-ray spectral fit to all clusters in a subsample simultaneously, assuming self-similarity of the temperature profile. This approach allows us to constrain the shape of the temperature profile over 0 < r < 1.5R500, which would be impossible on a per-cluster basis, since the observations of individual clusters have, on average, 2000 X-ray counts. The results presented here represent the first constraints on the evolution of the average temperature profile from z = 0 to z = 1.2. We find that high-z (0.6 < z < 1.2) clusters are slightly (∼30%) cooler both in the inner (r < 0.1R500) and outer (r > R500) regions than their low-z (0.3 < z < 0.6) counterparts. Combining the average temperature profile with measured gas density profiles from our earlier work, we infer the average pressure and entropy profiles for each subsample. Confirming earlier results from this data set, we find an absence of strong cool cores at high z, manifested in this analysis as a significantly lower observed pressure in the central 0.1R500 of the high-z cool-core subset of clusters compared to the low-z cool-core subset. Overall, our observed pressure profiles agree well with earlier lower-redshift measurements, suggesting minimal redshift evolution in the pressure profile outside of the core. We find no measurable redshift evolution in the entropy profile at r . 0.7R500 – this may reflect a long-standing balance between cooling and feedback over long timescales and large physical scales. We observe a slight flattening of the entropy profile at r & R500 in our high-z subsample. This flattening is consistent with a temperature bias due to the enhanced (∼3×) rate at which group-mass (∼2 keV) halos, which would go undetected at our survey depth, are accreting onto the cluster at z ∼ 1. This work demonstrates a powerful method for inferring spatially-resolved cluster properties in the case where individual cluster signal-to-noise is low, but the number of observed clusters is high.Publication Identification of Molecular Compartments and Genetic Circuitry in the Developing Mammalian Kidney(Company of Biologists, 2012) Duah, Mary; Staser, Karl; Valerius, Michael; Hansard, Jennifer K.; Guo, Jin-jin; McMahon, Jill Ann; Vaughan, Joseph; Faria, Diane; Georgas, Kylie; Rumballe, Bree; Ren, Qun; Krautzberger, A. Michaela; Junker, Jan P.; Thiagarajan, Rathi D.; Machanick, Philip; Gray, Paul A.; van Oudenaarden, Alexander; Rowitch, David H.; Stiles, Charles; Ma, Qiufu; Grimmond, Sean M.; Bailey, Timothy L.; Little, Melissa H.; McMahon, Andrew P.; Yu, JingLengthy developmental programs generate cell diversity within an organotypic framework, enabling the later physiological actions of each organ system. Cell identity, cell diversity and cell function are determined by cell type-specific transcriptional programs; consequently, transcriptional regulatory factors are useful markers of emerging cellular complexity, and their expression patterns provide insights into the regulatory mechanisms at play. We performed a comprehensive genome-scale in situ expression screen of 921 transcriptional regulators in the developing mammalian urogenital system. Focusing on the kidney, analysis of regional-specific expression patterns identified novel markers and cell types associated with development and patterning of the urinary system. Furthermore, promoter analysis of synexpressed genes predicts transcriptional control mechanisms that regulate cell differentiation. The annotated informational resource (www.gudmap.org) will facilitate functional analysis of the mammalian kidney and provides useful information for the generation of novel genetic tools to manipulate emerging cell populations.Publication An ES Cell System for Rapid, Spatial and Temporal Analysis of Gene Function in vitro and in vivo(Oxford University Press, 2005) Mao, Junhao; Barrow, Jeffery; McMahon, Jill Ann; Vaughan, Joe; McMahon, Andrew P.We describe a versatile genetic system for rapid analysis of mammalian gene function. In this, loss of reporter activity in a novel embryonic stem (ES) cell line enables rapid identification of targeting to the ubiquitously expressed Rosa26 locus. Subsequent regulation of gene activity is governed by a dual regulatory strategy utilizing two drugs, Tamoxifen and Doxycycline. To illustrate this approach, a dominant allele of Smoothened was introduced into this cell line, enabling regulated activation of Hedgehog signaling. By coupling Cre-loxP dependent activation with tetracycline dependent transcription in a single allele, we established a conditional method to control Smoothened activity and neural progenitor specification in differentiating ES cells in vitro and in chimeric embryos in vivo When crossed to an appropriate Cre driver strain, gene activity can also be temporally regulated within a specific cell lineage. This platform will facilitate rapid analysis of gene function in the mouse.