Digits in a dish: An in vitro system to assess the molecular genetics of hand/foot development at single-cell resolution.
Digits in a dish: An in vitro system to assess the molecular genetics of hand/foot development at single-cell resolution.
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DOI：
10.3389/fcell.2023.1135025
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
体外模型允许研究胚胎外的发育过程。为了获得介导手指和关节发育的细胞，我们鉴定了从远端早期自足动物分离的未分化间充质的独特性质，以自主重新组装形成多个自足动物结构，包括：手指、趾间组织、关节、肌肉和肌腱。这些发育结构的单细胞转录组学分析揭示了表达远端肢体发育的典型标志物的不同细胞簇，包括：Col 2a 1、Col 10a 1和Sp 7（方阵形成），Thbs 2和Col 1a 1（软骨膜）、Gdf 5、Wnt 5a和Jun（联合区间）、Aldh 1a 2和Msx 1（趾间组织）、Myod 1（肌肉祖细胞）、Prg 4（关节软骨膜/关节软骨）以及Scx和Tnmd（腱细胞/肌腱）。这些签名基因的基因表达模式的分析表明，发育时间和组织特异性定位也重演的方式类似的启动和成熟的发展中小鼠autopod。最后，体外指系统还概括了与基因突变相关的先天性畸形，因为Hoxa 13突变间充质的体外培养物产生了Hoxa 13突变体自足类动物中存在的缺陷，包括指融合、指骨节数减少和间充质凝聚不良。这些发现证明了体外手指系统重现手指和关节发育的稳健性。作为小鼠指和关节发育的体外模型，该创新系统将提供对发育中的肢体组织的访问，从而促进研究以辨别指和关节关节形成是如何启动的以及未分化的间充质是如何形成图案以建立个体指形态的。体外手指系统还提供了一个平台，用于快速评估旨在刺激受先天性畸形、损伤或疾病影响的哺乳动物手指修复或再生的治疗。
In vitro models allow for the study of developmental processes outside of the embryo. To gain access to the cells mediating digit and joint development, we identified a unique property of undifferentiated mesenchyme isolated from the distal early autopod to autonomously re-assemble forming multiple autopod structures including: digits, interdigital tissues, joints, muscles and tendons. Single-cell transcriptomic analysis of these developing structures revealed distinct cell clusters that express canonical markers of distal limb development including: Col2a1, Col10a1, and Sp7 (phalanx formation), Thbs2 and Col1a1 (perichondrium), Gdf5, Wnt5a, and Jun (joint interzone), Aldh1a2 and Msx1 (interdigital tissues), Myod1 (muscle progenitors), Prg4 (articular perichondrium/articular cartilage), and Scx and Tnmd (tenocytes/tendons). Analysis of the gene expression patterns for these signature genes indicates that developmental timing and tissue-specific localization were also recapitulated in a manner similar to the initiation and maturation of the developing murine autopod. Finally, the in vitro digit system also recapitulates congenital malformations associated with genetic mutations as in vitro cultures of Hoxa13 mutant mesenchyme produced defects present in Hoxa13 mutant autopods including digit fusions, reduced phalangeal segment numbers, and poor mesenchymal condensation. These findings demonstrate the robustness of the in vitro digit system to recapitulate digit and joint development. As an in vitro model of murine digit and joint development, this innovative system will provide access to the developing limb tissues facilitating studies to discern how digit and articular joint formation is initiated and how undifferentiated mesenchyme is patterned to establish individual digit morphologies. The in vitro digit system also provides a platform to rapidly evaluate treatments aimed at stimulating the repair or regeneration of mammalian digits impacted by congenital malformation, injury, or disease.
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DOI：
10.1073/pnas.1919470117
发表时间：
2020-01-14
影响因子：
11.1
作者：
Bastida, Maria Felix;Perez-Gomez, Rocio;Ros, Marian A.
通讯作者：
Ros, Marian A.
影响因子：
2.7
作者：
Bruneau, S;Johnson, KR;Duboule, D
通讯作者：
Duboule, D
影响因子：
3.7
作者：
Chatterjee, Sreoshi;Bhardwaj, Nitin;Saxena, Rajiv K.
通讯作者：
Saxena, Rajiv K.
DOI：
10.1016/j.cub.2021.09.010
发表时间：
2021-11-22
期刊：
Current biology : CB
影响因子：
--
作者：
Trofka A;Huang BL;Zhu J;Heinz WF;Magidson V;Shibata Y;Shi YB;Tarchini B;Stadler HS;Kabangu M;Al Haj Baddar NW;Voss SR;Mackem S
通讯作者：
Mackem S
影响因子：
4.7
作者：
Chen LH;Liu JF;Lu Y;He XY;Zhang C;Zhou HH
通讯作者：
Zhou HH