In Vivo Physiological Transdifferentiation of Adult Adipose Cells
In Vivo Physiological Transdifferentiation of Adult Adipose Cells
复制标题
DOI：
10.1002/stem.197
复制
发表时间：
2009-11-01
期刊：
影响因子：
5.2
通讯作者：
Cinti, Saverio
中科院分区：
文献类型：
--
作者：
De Matteis, Rita;Zingaretti, Marcia Cristina;Cinti, Saverio
来自身体不同部位的成年 Rosa26 小鼠的脂肪组织移植物，无论供体的性别如何，与乳腺脂肪一样，当暴露于怀孕和哺乳期雌性乳腺的微环境时，会产生泌乳上皮细胞。为了排除标记的乳腺组织源自与移植物的基质血管部分相关的干细胞的可能性，我们将通过用胶原酶处理脂肪组织片段获得的纯脂肪细胞悬浮液注射到乳腺中。将X-gal阳性细胞插入天然腺体的肺泡中，电镜显示标记的细胞已转化为泌乳腺细胞。在脂肪细胞注射部位，标记的肺泡含有 X-gal 阳性和 X-gal 阴性细胞的混合物，并且单个上皮细胞偶尔会在其他未标记的肺泡中染色。这表明生长的导管单独招募相邻的脂肪细胞，当它们成为腺泡的一部分时，这些脂肪细胞转分化为分泌性上皮细胞。解离后，分离的脂肪细胞保留了分化脂肪细胞典型的形态和蛋白质标记，但表达高水平的干细胞基因和重编程转录因子 Klf4。因此，与脂肪组织的基质血管成分相关的前脂肪细胞的成骨、软骨形成、肌源性和血管生成转化有充分记录，可能反映了脂肪细胞重新编程其基因表达并转化为不同细胞型的内在能力。干细胞2009； 27：2761-2768
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. STEM CELLS 2009; 27: 2761-2768