2024-03-21 カリフォルニア大学校アーバイン校(UCI)
◆カリフォルニア大学アーバイン校が主導した新しい研究は、米国で毎年生まれる赤ちゃんの約3%に影響する先天性奇形の起源に関する基本的な知識の変化を明らかにしました。この発見は、早期発見と予防戦略の新たな探求の道を提供します。
◆研究は、最近オンラインで発表されたScience Advances誌に掲載されました。Nipbl遺伝子とNanog遺伝子の複雑な相互作用に関する深刻な発見をし、これらの遺伝子の調節が早期胚発生および多くの組織や器官の発達に及ぼす影響を明らかにしました。
<関連情報>
- https://news.uci.edu/2024/03/21/uc-irvine-led-study-unlocks-the-secrets-of-birth-defect-origins/
- https://www.science.org/doi/10.1126/sciadv.adl4239
Nipbl+/-マウス胚における胚形成期の遺伝子発現は症候群性先天異常の発生を予見させる Gastrulation-stage gene expression in Nipbl+/- mouse embryos foreshadows the development of syndromic birth defects
STEPHENSON CHEA , JESSE KREGER , MARTHA E. LOPEZ-BURKS, ADAM L. MACLEAN , […], AND ANNE L. CALOF
Science Advances Published:20 Mar 2024
DOI:https://doi.org/10.1126/sciadv.adl4239
Abstract
In animal models, Nipbl deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange syndrome, the most common cause of which is Nipbl haploinsufficiency. Previous studies in Nipbl+/- mice suggested that heart development is abnormal as soon as cardiogenic tissue is formed. To investigate this, we performed single-cell RNA sequencing on wild-type and Nipbl+/- mouse embryos at gastrulation and early cardiac crescent stages. Nipbl+/- embryos had fewer mesoderm cells than wild-type and altered proportions of mesodermal cell subpopulations. These findings were associated with underexpression of genes implicated in driving specific mesodermal lineages. In addition, Nanog was found to be overexpressed in all germ layers, and many gene expression changes observed in Nipbl+/- embryos could be attributed to Nanog overexpression. These findings establish a link between Nipbl deficiency, Nanog overexpression, and gene expression dysregulation/lineage misallocation, which ultimately manifest as birth defects in Nipbl+/- animals and Cornelia de Lange syndrome.
