Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells

doi:10.1073/pnas.0532693100

Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells

^*Stem Cell Institute, Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55445; and ^‡Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55445

Edited by Darwin J. Prockop, Tulane University, New Orleans, LA, and approved January 10, 2003 (received for review May 6, 2002)

Abstract

Single human bone marrow-derived mesodermal progenitor cells (MPCs) differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and endothelial cells. To identify genes involved in the commitment of MPCs to osteoblasts we examined the expressed gene profile of undifferentiated MPCs and MPCs induced to the osteoblast lineage for 1–7 days by cDNA microarray analysis. As expected, growth factor, hormone, and signaling pathway genes known to be involved in osteogenesis were activated during differentiation. In addition, 41 transcription factors (TFs) were differentially expressed over time, including TFs with known roles in osteoblast differentiation and TFs not known to be involved in osteoblast differentiation. As the latter group of TFs coclustered with osteogenesis-specific TFs, they may play a role in osteoblast differentiation. When we compared the gene expression profile of MPCs induced to differentiate to chondroblasts and osteoblasts, significant differences in the nature and/or timing of gene activation were seen. These studies indicate that in vitro differentiation cultures in which MPCs are induced to one of multiple cell fates should be very useful for defining signals important for lineage-specific differentiation.

Footnotes

↵ † Present address: Pharmacia Corporation, Chesterfield, MO 63198.
↵ § To whom correspondence should be addressed. E-mail: verfa001{at}umn.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

MPC,

mesodermal progenitor cell;

TF,

transcription factor;

Cbfa1,

core binding factor alpha 1;

MSX2,

muscle segment homolog Drosophilia homeobox 2;

TGF,

transforming growth factor;

BMP,

bone morphogenetic protein;

KLF,

Kruppel-like factor;

TNF,

tumor necrosis factor;

AP,

alkaline phosphatase