PDGF, tgf- 2. And FGF signaling is important for differentiation and growth of mesenchymal stem cells (mscs)

Transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages

Felicia Ng, Shayne Boucher, Susie Koh, Seetharama S. Konduru, Lucas Chase, Uma Lakshmipathy, Cleo Choong, Zheng Yang, Mohan C. Vemuri, Mahendra S. Rao, Vivek Tanavde

Research output: Contribution to journalArticle

360 Citations (Scopus)

Abstract

We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)-β signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-β, PDGF, and β-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.

Original languageEnglish
Pages (from-to)295-307
Number of pages13
JournalBlood
Volume112
Issue number2
DOIs
Publication statusPublished - 15 Jul 2008
Externally publishedYes

Fingerprint

Fibroblast Growth Factors
Platelet-Derived Growth Factor
Stem cells
Mesenchymal Stromal Cells
Growth
Cell growth
Transforming Growth Factors
Osteocytes
Activins
Serum-Free Culture Media
Cell Surface Receptors
Gene Expression Profiling
Cell Lineage
Microarrays
Chondrocytes
Transcriptome
Adipocytes
Gene expression
Cell Differentiation
Bone Marrow

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

PDGF, tgf- 2. And FGF signaling is important for differentiation and growth of mesenchymal stem cells (mscs) : Transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. / Ng, Felicia; Boucher, Shayne; Koh, Susie; Konduru, Seetharama S.; Chase, Lucas; Lakshmipathy, Uma; Choong, Cleo; Yang, Zheng; Vemuri, Mohan C.; Rao, Mahendra S.; Tanavde, Vivek.

In: Blood, Vol. 112, No. 2, 15.07.2008, p. 295-307.

Research output: Contribution to journalArticle

Ng, Felicia ; Boucher, Shayne ; Koh, Susie ; Konduru, Seetharama S. ; Chase, Lucas ; Lakshmipathy, Uma ; Choong, Cleo ; Yang, Zheng ; Vemuri, Mohan C. ; Rao, Mahendra S. ; Tanavde, Vivek. / PDGF, tgf- 2. And FGF signaling is important for differentiation and growth of mesenchymal stem cells (mscs) : Transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. In: Blood. 2008 ; Vol. 112, No. 2. pp. 295-307.
@article{96542721f6c640f2a16d24bcdce26fe5,
title = "PDGF, tgf- 2. And FGF signaling is important for differentiation and growth of mesenchymal stem cells (mscs): Transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages",
abstract = "We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)-β signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-β, PDGF, and β-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.",
author = "Felicia Ng and Shayne Boucher and Susie Koh and Konduru, {Seetharama S.} and Lucas Chase and Uma Lakshmipathy and Cleo Choong and Zheng Yang and Vemuri, {Mohan C.} and Rao, {Mahendra S.} and Vivek Tanavde",
year = "2008",
month = "7",
day = "15",
doi = "10.1182/blood-2007-07-103697",
language = "English",
volume = "112",
pages = "295--307",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - PDGF, tgf- 2. And FGF signaling is important for differentiation and growth of mesenchymal stem cells (mscs)

T2 - Transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages

AU - Ng, Felicia

AU - Boucher, Shayne

AU - Koh, Susie

AU - Konduru, Seetharama S.

AU - Chase, Lucas

AU - Lakshmipathy, Uma

AU - Choong, Cleo

AU - Yang, Zheng

AU - Vemuri, Mohan C.

AU - Rao, Mahendra S.

AU - Tanavde, Vivek

PY - 2008/7/15

Y1 - 2008/7/15

N2 - We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)-β signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-β, PDGF, and β-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.

AB - We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)-β signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-β, PDGF, and β-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.

UR - http://www.scopus.com/inward/record.url?scp=47649121002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47649121002&partnerID=8YFLogxK

U2 - 10.1182/blood-2007-07-103697

DO - 10.1182/blood-2007-07-103697

M3 - Article

VL - 112

SP - 295

EP - 307

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -