The proliferation and development of hematopoietic cells occurs in clo
se association with bone marrow stroma. Heparan sulfate is a major com
ponent of the stroma. We have isolated a form of heparan sulfate prote
oglycan from a human stromal cell line grown in vitro in the presence
of [S-35]sulfate. This proteoglycan contains a phosphatidylinositol co
mponent which likely anchors it to the stromal cell membrane, The glyc
osaminoglycan chains of this proteoglycan could induce maturation of t
he HL-60 myeloid leukemia cell line. A less hydrophobic heparan sulfat
e proteoglycan was also present in the stroma, but could not induce HL
-60 maturation. The two heparan sulfates had glycosaminoglycan chains
that were similar in size (36 Kd) and charge density. Structural studi
es suggested only minor but perhaps significant differences in the car
bohydrate sequences of the two heparan sulfates. The relationship of t
hese subtle structural differences to the difference observed in diffe
rentiation-inducing activity remains to be elucidated.