心臓形成の3D映像を過去最早で撮影(Scientists film the heart forming in 3D earlier than ever)

ad

2025-05-12 ユニバーシティ・カレッジ・ロンドン(UCL)

UCLとフランシス・クリック研究所の研究チームは、マウス胚内で心臓が形成される過程をリアルタイムで3D撮影し、心筋細胞の起源を特定しました。この研究では、特殊なマウスモデルと先進的なライトシート顕微鏡を用いて、胚発生初期の「原腸形成」から原始心臓の形成までの約40時間を2分間隔で撮影。蛍光マーカーで標識された心筋細胞の動きを追跡し、心臓を構成する細胞系譜を明らかにしました。従来、心臓の細胞運命は後期に決定されると考えられていましたが、本研究は、心臓専用の細胞が原腸形成初期に出現し、秩序だった動きを示すことを示しています。この成果は、先天性心疾患の理解や再生医療への応用が期待され、『The EMBO Journal』に掲載されました。

<関連情報>

哺乳類の胃形成期における細胞移動と心臓運命決定の早期調整 Early coordination of cell migration and cardiac fate determination during mammalian gastrulation

Shayma Abukar, Peter A Embacher, Alessandro Ciccarelli, Sunita Varsani-Brown, Isabel G W North, Jamie A Dean, James Briscoe, and Kenzo Ivanovitch
The EMBO Journal  Published:13 May 2025
DOI:https://doi.org/10.1038/s44318-025-00441-0

Abstract

During gastrulation, mesodermal cells derived from distinct regions are destined to acquire specific cardiac fates after undergoing complex migratory movements. Here, we used light-sheet imaging of live mouse embryos between gastrulation and heart tube formation to track mesodermal cells and to reconstruct lineage trees and 3D migration paths for up to five cell divisions. We found independent progenitors emerging at specific times, contributing exclusively to left ventricle/atrioventricular canal (LV/AVC) or atrial myocytes. LV/AVC progenitors differentiated early to form the cardiac crescent, while atrial progenitors later generated the heart tube’s Nr2f2+ inflow tract during morphogenesis. We also identified short-lived multipotent progenitors with broad potential, illustrating early developmental plasticity. Descendants of multipotent progenitors displayed greater dispersion and more diverse migratory trajectories within the anterior mesoderm than the progeny of uni-fated progenitors. Progenitors contributing to extraembryonic mesoderm (ExEm) exhibited the fastest and most dispersed migrations. In contrast, those giving rise to endocardial, LV/AVC, and pericardial cells showed a more gradual divergence, with late-stage behavioural shifts: endocardial cells increased in speed, while pericardial cells slowed down in comparison to LV/AVC cells. Together, these data reveal patterns of individual cell directionality and cardiac fate allocation within the seemingly unorganised migratory pattern of mesoderm cells.

Synopsis

心臓形成の3D映像を過去最早で撮影(Scientists film the heart forming in 3D earlier than ever)

Progenitor cells that will contribute to formation of specific heart tissues are derived from distinct regions of the primitive streak in the developing mouse embryo. This study utilizes light-sheet microscopy in mouse embryos to track individual mesodermal cells destined to the heart for up to 40 h, revealing dynamic behaviours and lineages from gastrulation to heart tube formation.

•The left ventricle progenitors originate from early proximal mesoderm, while atrial progenitors are derived from late proximal mesoderm.

•Left ventricle progenitors differentiate early into myocytes, forming the cardiac crescent, while atrial progenitors differentiate later to establish the heart tube’s Nr2f2+ inflow regions.

•Most early proximal mesodermal cells are uni-fated and contribute predominantly to myocytes.

•Multi-potent progenitors are present and rapidly commit to specific cardiac fates as they migrate toward defined embryonic regions.

•Pairs of sister cells generated by uni-fated progenitors exhibit more coordinated migration paths compared to descendants of multi-potent progenitors.

細胞遺伝子工学
ad
ad
Follow
ad
タイトルとURLをコピーしました