In vivo physiological transdifferentiation of adult adipose cells.
Grafts of adipose tissue from adult Rosa26 mice from different sites of the body, irrespective of the sex of the donor, share with the mammary fat the property of giving rise to milk-secreting epithelial cells when exposed to the microenvironment of the mammary gland in pregnant and lactating females. To rule out the possibility that the labeled mammary glandular tissue was derived from stem cells associated with the stroma vascular part of the grafts, we injected into the mammary gland a pure suspension of adipocytes obtained by treating a fragment of adipose tissue with collagenase. X-gal-positive cells were inserted into the alveoli of the native gland, and electron microscopy showed that the labeled cells had transformed into milk-secreting glandular cells. At the site of the adipocyte injection, the labeled alveoli contained a mixture of X-gal-positive and X-gal-negative cells, and a single epithelial cell was occasionally stained in an otherwise unlabeled alveolus. This suggests that growing ducts individually recruit adjacent adipocytes that transdifferentiate into secretory epithelial cells as they became part of the glandular alveoli. After dissociation, the isolated adipocytes retained the morphology and protein markers typical of differentiated fat cells but expressed high levels of stem cell genes and the reprogramming transcription factor Klf4. Thus, the well-documented osteogenic, chondrogenic, myogenic, and angiogenic transformation of preadipocytes associated with the stroma vascular component of the adipose tissue may reflect an intrinsic capability of adipocytes to reprogram their gene expression and transform into different cytotypes.
De Matteis
Rita
R
Department of Molecular Pathology and Innovative Therapies, Faculty of Medicine, University of Ancona (Politecnica delle Marche), 60020-Ancona, Italy.
Zingaretti
Marcia Cristina
MC
Murano
Incoronata
I
Vitali
Alessandra
A
Frontini
Andrea
A
Giannulis
Ioanis
I
Barbatelli
Giorgio
G
Marcucci
Francesco
F
Bordicchia
Marica
M
Sarzani
Riccardo
R
Raviola
Elio
E
Cinti
Saverio
S
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D054338:Cell Transdifferentiation; D005260:Female; D007150:Immunohistochemistry; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D007774:Lactation / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D018800:Thy-1 Antigens / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; D018800:Thy-1 Antigens; D014157:Transcription Factors; D017493:Leukocyte Common Antigens