TY - JOUR
T1 - Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells
AU - Chan, Charles K.F.
AU - Lindau, Paul
AU - Jiang, Wen
AU - Chen, James Y.
AU - Zhang, Lillian F.
AU - Chen, Ching Cheng
AU - Seita, Jun
AU - Sahoo, Debashis
AU - Kim, Jae Beom
AU - Lee, Andrew
AU - Park, Sujin
AU - Nag, Divya
AU - Gong, Yongquan
AU - Kulkarni, Subhash
AU - Luppen, Cynthia A.
AU - Theologis, Alexander A.
AU - Wan, Derrick C.
AU - DeBoer, Anthony
AU - Seo, Eun Young
AU - Vincent-Tompkins, Justin D.
AU - Loh, Kyle
AU - Walmsley, Graham G.
AU - Kraft, Daniel L.
AU - Wu, Joseph C.
AU - Longaker, Michael T.
AU - Weissman, Irving L.
PY - 2013/7/30
Y1 - 2013/7/30
N2 - Organs are composites of tissue types with diverse developmental origins, and they rely on distinct stem and progenitor cells to meet physiological demands for cellular production and homeostasis. How diverse stem cell activity is coordinated within organs is not well understood. Here we describe a lineage-restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal progenitor; BCSP) isolated from limb bones and bonemarrow tissue of fetal, neonatal, and adult mice. The BCSP clonally produces chondrocytes (cartilage-forming) and osteogenic (bone-forming) cells and at least three subsets of stromal cells that exhibit differential expression of cell surface markers, including CD105 (or endoglin), Thy1 [or CD90 (cluster of differentiation 90)], and 6C3 [ENPEP glutamyl aminopeptidase (aminopeptidase A)]. These three stromal subsets exhibit differential capacities to support hematopoietic (blood-forming) stem and progenitor cells. Although the 6C3-expressing subset demonstrates functional stem cell niche activity by maintaining primitive hematopoietic stem cell (HSC) renewal in vitro, the other stromal populations promote HSC differentiation to more committed lines of hematopoiesis, such as the B-cell lineage. Gene expression analysis and microscopic studies further reveal a microenvironment in which CD105-, Thy1-, and 6C3-expressing marrow stroma collaborate to provide cytokine signaling to HSCs and more committed hematopoietic progenitors. As a result, within the context of bone as a blood-forming organ, the BCSP plays a critical role in supporting hematopoiesis through its generation of diverse osteogenic and hematopoietic-promoting stroma, including HSC supportive 6C3(+) niche cells.
AB - Organs are composites of tissue types with diverse developmental origins, and they rely on distinct stem and progenitor cells to meet physiological demands for cellular production and homeostasis. How diverse stem cell activity is coordinated within organs is not well understood. Here we describe a lineage-restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal progenitor; BCSP) isolated from limb bones and bonemarrow tissue of fetal, neonatal, and adult mice. The BCSP clonally produces chondrocytes (cartilage-forming) and osteogenic (bone-forming) cells and at least three subsets of stromal cells that exhibit differential expression of cell surface markers, including CD105 (or endoglin), Thy1 [or CD90 (cluster of differentiation 90)], and 6C3 [ENPEP glutamyl aminopeptidase (aminopeptidase A)]. These three stromal subsets exhibit differential capacities to support hematopoietic (blood-forming) stem and progenitor cells. Although the 6C3-expressing subset demonstrates functional stem cell niche activity by maintaining primitive hematopoietic stem cell (HSC) renewal in vitro, the other stromal populations promote HSC differentiation to more committed lines of hematopoiesis, such as the B-cell lineage. Gene expression analysis and microscopic studies further reveal a microenvironment in which CD105-, Thy1-, and 6C3-expressing marrow stroma collaborate to provide cytokine signaling to HSCs and more committed hematopoietic progenitors. As a result, within the context of bone as a blood-forming organ, the BCSP plays a critical role in supporting hematopoiesis through its generation of diverse osteogenic and hematopoietic-promoting stroma, including HSC supportive 6C3(+) niche cells.
KW - Endochondral ossification
KW - Lymphopoiesis
UR - http://www.scopus.com/inward/record.url?scp=84881095160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881095160&partnerID=8YFLogxK
U2 - 10.1073/pnas.1310212110
DO - 10.1073/pnas.1310212110
M3 - Article
C2 - 23858471
AN - SCOPUS:84881095160
SN - 0027-8424
VL - 110
SP - 12643
EP - 12648
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -