Targeting the bone marrow with activin A-overexpressing embryonic multipotent stromal cells specifically modifies B lymphopoiesis.
In vitro and in vivo studies implicate a series of cytokines in regulation of lymphohematopoiesis. However, direct indications for a local role of most of these cytokines within the bone marrow is lacking. In the present study, we aimed to test the contribution of a specific cytokine, activin A, a member of the transforming growth factor-beta (TGF-beta) family, to lymphohematopoiesis in mouse bone marrow. We show that mouse embryonic fibroblasts (MEFs) are indistinguishable from multipotent stromal cells (MSCs). Such MEFs overexpressing activin A, supported in vitro myelopoiesis in long-term bone marrow cultures as effectively as control MEFs. In contrast, activin A-overexpressing MEFs interfered with the in vitro generation of B lineage cells in such cultures. Thus, excessive expression in vitro of activin A, by supportive stromal cells, causes preferential maturation of myeloid rather than lymphoid cells. Moreover, the activin A-overexpressing MEFs caused an increased incidence in vivo of relatively immature B lineage cells; upon transplantation through the spleen route, MEFs engrafted the bone marrow specifically. Activin A-overexpressing MEFs accumulated in the bone marrow compartment and slowed down the progression of B cell precursors along the differentiation pathway, while sparing the myeloid population. The assay system described in this paper provides a means to assess the contribution of a wide range of molecules to hematopoiesis without perturbing the constitution of other organs.
Parameswaran
Reshmi
R
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Morad
Vered
V
Laronne
Ayelet
A
Rousso-Noori
Liat
L
Shani
Nir
N
Naffar-Abu-Amara
Suha
S
Zipori
Dov
D
D028341:Activins / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D039902:Multipotent Stem Cells; D017154:Stromal Cells / Q000378:metabolism*
C422405:activin A; D028341:Activins