NDLI: Myb permits multilineage airway epithelial cell differentiation.

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Myb permits multilineage airway epithelial cell differentiation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pan, Jie-Hong Adair-Kirk, Tracy L. Patel, Anand C. Huang, Tao Yozamp, Nicholas S. Xu, Jian Reddy, E. Premkumar Byers, Derek E. Pierce, Richard A. Holtzman, Michael J. Brody, Steven L.
Description	Country affiliation: United States Author Affiliation: Pan JH ( Department of Medicine, Washington University, St. Louis, Missouri, USA.)
Abstract	The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63(+) basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps are poorly defined. Here, we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb(+) cells were identified as p63(-) and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63(-) population with failed maturation of Foxj1(+) ciliated cells as well as Scbg1a1(+) and Muc5ac(+) secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb(+) cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63(-) Myb(+) population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease.
File Format	HTM / HTML
ISSN	10665099
e-ISSN	15494918
DOI	10.1002/stem.1814
Journal	STEM CELLS
Issue Number	12
Volume Number	32
Language	English
Publisher	Wiley
Publisher Date	2014-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Discipline Embryology Cell Differentiation Physiology Cell Lineage Epithelial Cells Metabolism Epithelium Proto-oncogene Proteins C-myb Stem Cells Cytology Animals Cells, Cultured Mice Respiratory Mucosa Respiratory System Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Medicine

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