Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Actin depolymerization enhances adipogenic differentiation in human stromal stem cells. / Chen, Li; Hu, Huimin; Qiu, Weimin; Shi, Kaikai; Kassem, Moustapha.

In: Stem Cell Research, Vol. 29, 05.2018, p. 76-83.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chen, L, Hu, H, Qiu, W, Shi, K & Kassem, M 2018, 'Actin depolymerization enhances adipogenic differentiation in human stromal stem cells', Stem Cell Research, vol. 29, pp. 76-83. https://doi.org/10.1016/j.scr.2018.03.010

APA

Chen, L., Hu, H., Qiu, W., Shi, K., & Kassem, M. (2018). Actin depolymerization enhances adipogenic differentiation in human stromal stem cells. Stem Cell Research, 29, 76-83. https://doi.org/10.1016/j.scr.2018.03.010

Vancouver

Chen L, Hu H, Qiu W, Shi K, Kassem M. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells. Stem Cell Research. 2018 May;29:76-83. https://doi.org/10.1016/j.scr.2018.03.010

Author

Chen, Li ; Hu, Huimin ; Qiu, Weimin ; Shi, Kaikai ; Kassem, Moustapha. / Actin depolymerization enhances adipogenic differentiation in human stromal stem cells. In: Stem Cell Research. 2018 ; Vol. 29. pp. 76-83.

Bibtex

@article{9545d96c87cf439ea5c5ea4e60bdbabb,

title = "Actin depolymerization enhances adipogenic differentiation in human stromal stem cells",

abstract = "Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation.",

author = "Li Chen and Huimin Hu and Weimin Qiu and Kaikai Shi and Moustapha Kassem",

year = "2018",

month = may,

doi = "10.1016/j.scr.2018.03.010",

language = "English",

volume = "29",

pages = "76--83",

journal = "Stem Cell Research",

issn = "1873-5061",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

AU - Chen, Li

AU - Hu, Huimin

AU - Qiu, Weimin

AU - Shi, Kaikai

AU - Kassem, Moustapha

PY - 2018/5

Y1 - 2018/5

N2 - Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation.

AB - Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation.

U2 - 10.1016/j.scr.2018.03.010

DO - 10.1016/j.scr.2018.03.010

M3 - Journal article

C2 - 29605806

VL - 29

SP - 76

EP - 83

JO - Stem Cell Research

JF - Stem Cell Research

SN - 1873-5061

ER -

ID: 202070438