合成ヒト胚モデルの利用法

精子や卵子、子宮を使わずに、初期段階のヒト胚（受精卵）によく似た細胞の集合体「胚モデル」をつくり出したとする研究結果が、科学誌「ネイチャー」に6日、掲載された。

The ability to study human post-implantation development remains limited due to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (i.e., embryonic disk, bilaminar disk, yolk- and chorionic sacs, surrounding trophoblasts) remain lacking2. Mouse naïve embryonic stem cells (ESCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse Structured Stem cell-based Embryo Models with spatially organized morphogenesis (SEMs)3. Here, we extend these findings to humans, while using only genetically unmodified human naïve ESCs (in HENSM conditions)4. Such human fully integrated SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf) (Carnegie stage 6a). This includes embryonic disk and bilaminar disk formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, PGC specification, polarized yolk sac with visceral and parietal endoderm, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, a trophoblast surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform may enable the experimental interrogation of previously inaccessible windows of human early post-implantation up to peri-gastrulation development.

Our ability to study early human post-implantation development remains highly limited due to the ethical and technical challenges associated with intrauterine development of the human embryo after implantation. Despite the great progress made on human gastruloids, axioloids and in vitro cultured blastoids, such elegant models do not constitute an integrated Stem cell-derived Embryo Models (SEMs) that includes all the key extra-embryonic tissues of the early post-implantation human conceptus (e.g., hypoblast, yolk-sac, trophoblasts, amnion, and extraembryonic mesoderm), and thus, do not recapitulate post-implantation epiblast development within the context of these extra-embryonic compartments. Mouse naïve pluripotent stem cells (PSCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse SEMs, while bypassing the blastocyst-like stage, and eventually initiating organogenesis ex utero . Here, we implement critical adaptations to extend these finding to humans, while using only genetically unmodified human naïve PSCs, thus circumventing the need for ectopic expression of lineage promoting transgenes. Such integrated human SEMs recapitulate the organization of all known compartments of early post-implantation stage human embryos, including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity and a connective stalk. This new platform constitutes a tractable stem cell-based model for experimentally interrogating previously inaccessible windows of human peri- and early post-implantation development. ### Competing Interest Statement Declaration of interests: J.H.H has submitted patent applications relevant to the findings reported herein and is a chief scientific adviser of Renewal Bio Ltd. that has licensed technologies described herein and sponsored some parts of this project.

イスラエルの生物学者は、マウスの幹細胞を使って本物そっくりの人工胚を形成し、機械の子宮の中で数日間、成長させることに成功した。同氏が創業者に名を連ねるスタートアップ企業は、ヒトの細胞を使って人工胚を作り、移植用に初期の臓器や組織を採取する構想を持つ。

Renewing Human Health Our Publications: "Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis, Nature, 2021" "Post-Gastrulation Synthetic Embryos Generated Ex Utero from Mouse Naïve ESCs, Cell 2022"

画像クレジット:Ilia Yefimovich/picture-alliance/dpa/AP Images

神戸大学大学院人文学研究科の新川拓哉講師は、埼玉医科大学の林禅之助教、カールトン大学のジョシュア・シェパード准教授、京都大学高等研究院 ヒト生物学高等研究拠点（WPI-ASHBi）の澤井努特定助教と共同で、ヒト脳オルガノ...

Scientist with a Petri dish – Download this photo by Drew Hays on Unsplash