Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration.
Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration.
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DOI：
10.1126/science.aaq0681
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发表时间：
2018-10-26
期刊：
影响因子：
--
通讯作者：
Treutlein B
中科院分区：
文献类型：
--
作者：
Gerber T;Murawala P;Knapp D;Masselink W;Schuez M;Hermann S;Gac-Santel M;Nowoshilow S;Kageyama J;Khattak S;Currie JD;Camp JG;Tanaka EM;Treutlein B
蝾螈前肢的截肢导致胚基的形成，胚基是一种在肢体再生之前祖细胞积累的短暂组织。结缔组织（CT）-骨骼，周膜，肌腱，真皮，间质成纤维细胞-贡献了占胚基的绝大多数细胞，然而，目前还不清楚单个CT细胞如何重新编程它们的命运以重建四足动物肢体。在这里，我们使用Cre-loxP报告基因谱系追踪和单细胞（sc）RNA-seq的组合，首次在分子上追踪成体CT细胞异质性及其向肢体芽基状态的转变。我们发现了一个多相分子程序，其中在未受伤的成人肢体中发现的CT细胞类型恢复到相对同质的祖细胞状态，其在增殖、建立位置信息和最终再分化之前参与炎症和细胞外基质分解。虽然早期再生转录组状态是芽基所独有的，但后期阶段重演了胚胎肢体发育。值得注意的是，我们没有发现在未受伤的成人组织中预先存在的芽样前体或肢芽样祖细胞的证据。然而，我们发现，不同的CT亚群在成人肢体差异有助于延长骨在截肢平面与再生新的部分。我们的数据共同阐明了脊椎动物复杂器官再生过程中的分子和细胞重新编程。
Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. Connective tissue (CT) – skeleton, periskeleton, tendon, dermis, interstitial fibroblasts – contributes the vast majority of cells that populate the blastema, however, it is unclear how individual CT cells may reprogram their fate in order to rebuild the tetrapod limb. Here we use a combination of Cre-loxP reporter lineage tracking and single-cell (sc) RNA-seq to molecularly track, for the first time, adult CT cell heterogeneity and its transition to a limb blastema state. We uncover a multi-phasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that participates in inflammation and extracellular matrix disassembly prior to proliferation, establishment of positional information, and ultimately re-differentiation. While the early regeneration transcriptome states are unique to the blastema, the later stages recapitulate embryonic limb development. Notably, we do not find evidence of a pre-existing blastema-like precursor nor limb bud-like progenitors in the uninjured adult tissue. However, we find that distinct CT subpopulations in the adult limb differentially contribute to extending bone at the amputation plane versus regenerating new segments. Together, our data illuminates molecular and cellular reprogramming during complex organ regeneration in a vertebrate.
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DOI：
10.1002/reg2.16
发表时间：
2014-06
期刊：
Regeneration (Oxford, England)
影响因子：
--
作者：
Makanae A;Mitogawa K;Satoh A
通讯作者：
Satoh A
影响因子：
56.9
作者：
Gurevich, David B.;Phong Dang Nguyen;Currie, Peter D.
通讯作者：
Currie, Peter D.
影响因子：
4.6
作者：
Arques, Carlos G.;Doohan, Roisin;Torres, Miguel
通讯作者：
Torres, Miguel
影响因子：
7.8
作者：
BouGharios, G;Garrett, LA;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
影响因子：
14.8
作者：
Khattak, Shahryar;Murawala, Prayag;Tanaka, Elly M.
通讯作者：
Tanaka, Elly M.