Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution

Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution
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DOI:
10.1038/s41467-018-07604-0
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发表时间:
2018-12-04
影响因子:
16.6
通讯作者:
Whited, Jessica L.
Whited, Jessica L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Leigh, Nicholas D.;Dunlap, Garrett S.;Whited, Jessica L.

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复杂的多组织结构(如四肢)的再生需要多种细胞类型的协调努力。在蝾螈肢体再生中,伤口表皮和芽基已经通过组织学、移植和大量组织RNA测序进行了广泛的研究。然而,由于有关再生肢体中细胞类型分子身份的信息有限,因此定义这些组织的贡献受到阻碍。在这里,我们报告了来自蝾螈肢体的25,000多个细胞的无偏见单细胞RNA测序,并在稳态和再生肢体中鉴定了表皮,间充质和造血谱系中的过多细胞多样性。我们确定了再生诱导基因,发展了胚基细胞分化的假定轨迹,并提出了成纤维细胞样胚基祖细胞的分子身份。这项工作将使分子技术的应用,以评估这些人口的肢体再生的贡献。总的来说,这些数据允许建立一个假定的框架,成年蝾螈肢体再生。
Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, defining the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. Here we report unbiased single-cell RNA-sequencing on over 25,000 cells from axolotl limbs and identify a plethora of cellular diversity within epidermal, mesenchymal, and hematopoietic lineages in homeostatic and regenerating limbs. We identify regeneration-induced genes, develop putative trajectories for blastema cell differentiation, and propose the molecular identity of fibroblast-like blastema progenitor cells. This work will enable application of molecular techniques to assess the contribution of these populations to limb regeneration. Overall, these data allow for establishment of a putative framework for adult axolotl limb regeneration.