In vivo physiological transdifferentiation of adult adipose cells

Rita De Matteis, Marcia Cristina Zingaretti, Incoronata Murano, Alessandra Vitali, Andrea Frontini, Ioanis Giannulis, Giorgio Barbatelli, Francesco Marcucci, Marica Bordicchia, Riccardo Sarzani, Elio Raviola, Saverio Cinti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2761-2768
Number of pages8
JournalStem Cells
Volume27
Issue number11
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Mammary epithelial cell
  • Reprogrammation
  • Transdifferentiation
  • White adipocytes
  • White adipose tissue

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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