{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:40:32Z","timestamp":1787593232621,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:italic>GNAS<\/jats:italic> encodes the stimulatory G protein alpha-subunit (Gs\u03b1) and its large variant XL\u03b1s. Studies have suggested that XL\u03b1s is expressed exclusively paternally. Thus, XL\u03b1s deficiency is considered to be responsible for certain findings in patients with paternal <jats:italic>GNAS<\/jats:italic> mutations, such as pseudo-pseudohypoparathyroidism, and the phenotypes associated with maternal uniparental disomy of chromosome 20, which comprises <jats:italic>GNAS<\/jats:italic>. However, a study of bone marrow stromal cells (BMSC) suggested that XL\u03b1s could be biallelically expressed. Aberrant BMSC differentiation due to constitutively activating <jats:italic>GNAS<\/jats:italic> mutations affecting both Gs\u03b1 and XL\u03b1s is the underlying pathology in fibrous dysplasia of bone. To investigate allelic XL\u03b1s expression, we employed next-generation sequencing and a polymorphism common to XL\u03b1s and Gs\u03b1, as well as A\/B, another paternally expressed <jats:italic>GNAS<\/jats:italic> transcript. In mouse BMSCs, Gs\u03b1 transcripts were 48.4 \u00b1 0.3% paternal, while A\/B was 99.8 \u00b1 0.2% paternal. In contrast, XL\u03b1s expression varied among different samples, paternal contribution ranging from 43.0 to 99.9%. Sample-to-sample variation in paternal XL\u03b1s expression was also detected in bone (83.7\u201399.6%) and cerebellum (83.8 to 100%) but not in cultured calvarial osteoblasts (99.1 \u00b1 0.1%). Osteoblastic differentiation of BMSCs shifted the paternal XL\u03b1s expression from 83.9 \u00b1 1.5% at baseline to 97.2 \u00b1 1.1%. In two human BMSC samples grown under osteoinductive conditions, XL\u03b1s expression was also predominantly monoallelic (91.3 or 99.6%). Thus, the maternal <jats:italic>GNAS<\/jats:italic> contributes significantly to XL\u03b1s expression in BMSCs but not osteoblasts. Altered XL\u03b1s activity may thus occur in certain cell types irrespective of the parental origin of a <jats:italic>GNAS<\/jats:italic> defect.<\/jats:p>","DOI":"10.3389\/fgene.2021.680537","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T09:20:10Z","timestamp":1623921610000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Maternal GNAS Contributes to the Extra-Large G Protein \u03b1-Subunit (XL\u03b1s) Expression in a Cell Type-Specific Manner"],"prefix":"10.3389","volume":"12","author":[{"given":"Qiuxia","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cagri","family":"Aksu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birol","family":"Ay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire E.","family":"Remillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius","family":"Plagge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Gardezi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Dunlap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis C.","family":"Gerstenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Bastepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gky379","article-title":"The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update.","volume":"46","author":"Afgan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/ajmg.10751","article-title":"Constitutional deletion of chromosome 20q in two patients affected with albright hereditary osteodystrophy.","volume":"113","author":"Aldred","year":"2002","journal-title":"Am. 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