{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:24:06Z","timestamp":1791343446184,"version":"4.3.1"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,11,4]]},"abstract":"<jats:p>\n                    Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that the heterotrimeric G protein \u03b1 subunit G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1 is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1 early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days of age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1 in cells of the osteoblast lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1-deficient osteoblasts, and exogenous IL-7 is able to restore B cell precursor populations in the bone marrow of mutant mice. Finally, the defect in B lymphopoiesis can be rescued by transplantation into a WT microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate\n                    <jats:italic>in vivo<\/jats:italic>\n                    that G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0802898105","type":"journal-article","created":{"date-parts":[[2008,10,28]],"date-time":"2008-10-28T22:24:31Z","timestamp":1225232671000},"page":"16976-16981","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":231,"title":["Osteoblastic regulation of B lymphopoiesis is mediated by G\n                    <sub>s<\/sub>\n                    \u03b1-dependent signaling pathways"],"prefix":"10.1073","volume":"105","author":[{"given":"Joy Y.","family":"Wu","sequence":"first","affiliation":[{"name":"Endocrine Unit and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise E.","family":"Purton","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Harvard Stem Cell Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Rodda","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"McMahon","sequence":"additional","affiliation":[{"name":"Harvard Stem Cell Institute and"},{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Scadden","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114;"},{"name":"Harvard Stem Cell Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry M.","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Endocrine Unit and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,11,4]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"7","article-title":"The relationship between the spleen colony-forming cell and the haemopoietic stem cell","volume":"4","author":"Schofield R","year":"1978","unstructured":"R Schofield, The relationship between the spleen colony-forming cell and the haemopoietic stem cell. 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