Progenitor cell formation from connective tissue during Axolotl limb regeneration

蝾螈肢体再生过程中结缔组织祖细胞的形成

• 批准号: 178725451
• 负责人: Professorin Dr. Elly Margaret Tanaka, Ph.D.
• 金额: --
• 依托单位: IMBA - Institute of Molecular Biotechnology GmbH
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/178725451?language=en
• 关键词: Progenitor; cell; formation; connective; tissue

Adult salamanders display functional regeneration of organs such as the eye, lower jaw, limb and tail, while mammals have lost this capacity. Which extracellular and intracellular factors determine a non-regenerative versus regenerative response to injury? In non-regenerating organisms, the wound site is infiltrated by connective tissue fibroblasts that contract the wound together, but these cells form scar tissue rather than replacing lost tissue. In contrast, during limb regeneration the connective tissue produces multipotent progenitor cells that express developmental genes and regenerate patterned skeleton. This proposal addresses how injury causes the salamander limb connective tissue to produce a multipotent progenitor cell that expresses developmental genes. Using cell tracking we will determine if connective tissue fibroblasts and cartilage dedifferentiate to a progenitor cell state, or whether a resident stem cell is selectively amplified. We will then determine which extracellular signals promote the formation of the progenitor cells. Finally, we will determine the epigenetic changes that occur at the genomic loci of developmental genes in the regenerating connective tissue.

成年蝾螈的眼睛、下颚、四肢和尾巴等器官都有功能性再生，而哺乳动物则失去了这种能力。哪些细胞外和细胞内因素决定了对损伤的非再生与再生反应？在非再生生物体中，伤口部位被结缔组织成纤维细胞浸润，这些成纤维细胞将伤口收缩在一起，但这些细胞形成疤痕组织而不是取代失去的组织。相反，在肢体再生过程中，结缔组织产生多能祖细胞，这些祖细胞表达发育基因并再生有图案的骨骼。该建议解决了损伤如何导致蝾螈四肢结缔组织产生表达发育基因的多能祖细胞。使用细胞跟踪，我们将确定结缔组织成纤维细胞和软骨是否去分化为祖细胞状态，或者是否有一个常驻干细胞被选择性扩增。然后我们将确定哪些细胞外信号促进祖细胞的形成。最后，我们将确定再生结缔组织中发育基因的基因组位点发生的表观遗传变化。

项目成果

Optimized axolotl (Ambystoma mexicanum) husbandry, breeding, metamorphosis, transgenesis and tamoxifen-mediated recombination

• DOI: 10.1038/nprot.2014.040
• 发表时间: 2014-03-01
• 期刊: NATURE PROTOCOLS
• 影响因子: 14.8
• 作者: Khattak, Shahryar;Murawala, Prayag;Tanaka, Elly M.
• 通讯作者: Tanaka, Elly M.

Connective tissue cells, but not muscle cells, are involved in establishing the proximo-distal outcome of limb regeneration in the axolotl

• DOI: 10.1242/dev.081752
• 发表时间: 2013-02-01
• 期刊: DEVELOPMENT
• 影响因子: 4.6
• 作者: Nacu, Eugen;Glausch, Mareen;Tanaka, Elly M.
• 通讯作者: Tanaka, Elly M.