title: Differentiated type II pneumocytes can be reprogrammed by ectopic Sox2 expression.
abstract: The adult lung contains several distinct stem cells, although their properties and full potential are still being sorted out. We previously showed that ectopic Sox2 expression in the developing lung manipulated the fate of differentiating cells. Here, we addressed the question whether fully differentiated cells could be redirected towards another cell type. Therefore, we used transgenic mice to express an inducible Sox2 construct in type II pneumocytes, which are situated in the distal, respiratory areas of the lung. Within three days after the induction of the transgene, the type II cells start to proliferate and form clusters of cuboidal cells. Prolonged Sox2 expression resulted in the reversal of the type II cell towards a more embryonic, precursor-like cell, being positive for the stem cell markers Sca1 and Ssea1. Moreover, the cells started to co-express Spc and Cc10, characteristics of bronchioalveolar stem cells. We demonstrated that Sox2 directly regulates the expression of Sca1. Subsequently, these cells expressed Trp63, a marker for basal cells of the trachea. So, we show that the expression of one transcription factor in fully differentiated, distal lung cells changes their fate towards proximal cells through intermediate cell types. This may have implications for regenerative medicine, and repair of diseased and damaged lungs.
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kapere Ochieng
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Schilders
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: Kool
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Marjon
authors.initials: M
authors.lastname: Buscop-van Kempen
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Boerema-De Munck
authors.affiliation: Department of Cell Biology of the Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Wijnen
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: Department of Pediatric Surgery of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; Department of Cell Biology of the Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Rottier
mesh_terms: D056809:Alveolar Epithelial Cells / Q000502:physiology*; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D054338:Cell Transdifferentiation; D065150:Cellular Reprogramming; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D061251:Primary Cell Culture; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse