Abstract
Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFR as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFR + cells represent a cell population distinct from CD56 + myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFR + population. Activation of PDGFR stimulates proliferation of PDGFR + cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFR + cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFR + mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.
| Original language | English |
|---|---|
| Article number | e1186 |
| Journal | Cell Death and Disease |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 04-2014 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research
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Identification and characterization of PDGFR + mesenchymal progenitors in human skeletal muscle. / Uezumi, A.; Fukada, S.; Yamamoto, N.; Ikemoto-Uezumi, M.; Nakatani, M.; Morita, M.; Yamaguchi, A.; Yamada, H.; Nishino, I.; Hamada, Y.; Tsuchida, K.
In: Cell Death and Disease, Vol. 5, No. 4, e1186, 04.2014.Research output: Contribution to journal › Article
TY - JOUR
T1 - Identification and characterization of PDGFR + mesenchymal progenitors in human skeletal muscle
AU - Uezumi, A.
AU - Fukada, S.
AU - Yamamoto, N.
AU - Ikemoto-Uezumi, M.
AU - Nakatani, M.
AU - Morita, M.
AU - Yamaguchi, A.
AU - Yamada, H.
AU - Nishino, I.
AU - Hamada, Y.
AU - Tsuchida, K.
PY - 2014/4
Y1 - 2014/4
N2 - Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFR as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFR + cells represent a cell population distinct from CD56 + myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFR + population. Activation of PDGFR stimulates proliferation of PDGFR + cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFR + cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFR + mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.
AB - Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFR as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFR + cells represent a cell population distinct from CD56 + myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFR + population. Activation of PDGFR stimulates proliferation of PDGFR + cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFR + cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFR + mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.
UR - http://www.scopus.com/inward/record.url?scp=84901045017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901045017&partnerID=8YFLogxK
U2 - 10.1038/cddis.2014.161
DO - 10.1038/cddis.2014.161
M3 - Article
C2 - 24743741
AN - SCOPUS:84901045017
VL - 5
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 4
M1 - e1186
ER -