TY - JOUR
T1 - Cell shape alteration during adipogenesis is associated with coordinated matrix cues
AU - Mor-Yossef Moldovan, Lisa
AU - Lustig, Maayan
AU - Naftaly, Alex
AU - Mardamshina, Mariya
AU - Geiger, Tamar
AU - Gefen, Amit
AU - Benayahu, Dafna
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/4
Y1 - 2019/4
N2 - Obesity has become one of the leading pathophysiologic disorders in recent years. Adipose tissue is the main tissue related to obesity and is known to play a role in various physiological complications, including type 2 diabetes. To better understand how the fat tissue develops, we used an in vitro live cell imaging system to quantify the adipogenesis by means of nondestructive digital imaging to monitor the accumulation of intracellular lipid droplets (LDs), a hallmark of adipogenesis, from the macro- to the micro-scale. Analyzing the cells’ shape at the single-cell level allows to quantify the cells’ shape change from a fibroblast to spherical morphology, indicating the start of adipogenesis. To reveal the molecular alterations, we applied a proteomic approach using high-resolution mass spectrometry of the proliferation, confluent fibroblasts and of adipocytes. During this process, we noted the reorganization of the cells’ extracellular matrix (ECM) network microenvironment from fibrillary collagen types I, III and V to collagens IV and VI, which affected the cells niche. The changes in ECM are translated for cytoskeleton remodeling according to cell fate-determining mechanisms. We quantified the cytoskeleton rearrangement of long oriented actin fibers or short cortical and disorganized fibers, associated with LDs accumulation in adipocytes. Developing in vitro models and analytical methods enable us to study differentiation into adipocytes that will advance our understanding regarding the niche conditions that affect adipogenesis. Consequently, this will enable the development of new modalities to prevent obesity and its deleterious outcomes and to develop potential treatments to battle pathophysiology-related diseases.
AB - Obesity has become one of the leading pathophysiologic disorders in recent years. Adipose tissue is the main tissue related to obesity and is known to play a role in various physiological complications, including type 2 diabetes. To better understand how the fat tissue develops, we used an in vitro live cell imaging system to quantify the adipogenesis by means of nondestructive digital imaging to monitor the accumulation of intracellular lipid droplets (LDs), a hallmark of adipogenesis, from the macro- to the micro-scale. Analyzing the cells’ shape at the single-cell level allows to quantify the cells’ shape change from a fibroblast to spherical morphology, indicating the start of adipogenesis. To reveal the molecular alterations, we applied a proteomic approach using high-resolution mass spectrometry of the proliferation, confluent fibroblasts and of adipocytes. During this process, we noted the reorganization of the cells’ extracellular matrix (ECM) network microenvironment from fibrillary collagen types I, III and V to collagens IV and VI, which affected the cells niche. The changes in ECM are translated for cytoskeleton remodeling according to cell fate-determining mechanisms. We quantified the cytoskeleton rearrangement of long oriented actin fibers or short cortical and disorganized fibers, associated with LDs accumulation in adipocytes. Developing in vitro models and analytical methods enable us to study differentiation into adipocytes that will advance our understanding regarding the niche conditions that affect adipogenesis. Consequently, this will enable the development of new modalities to prevent obesity and its deleterious outcomes and to develop potential treatments to battle pathophysiology-related diseases.
KW - ECM and cytoskeleton remodeling
KW - adipogenesis
KW - cell niche
KW - collagens
KW - mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=85052922858&partnerID=8YFLogxK
U2 - 10.1002/jcp.27157
DO - 10.1002/jcp.27157
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AN - SCOPUS:85052922858
SN - 0021-9541
VL - 234
SP - 3850
EP - 3863
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 4
ER -