Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?

Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?
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DOI:
10.1242/bio.058890
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发表时间:
2021-10-15
期刊:
影响因子:
2.4
通讯作者:
Johnson AD
Johnson AD
中科院分区:
生物学4区
文献类型:
--
作者:
Savage AM;Alberio R;Johnson AD

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组织特异性干细胞[例如造血干细胞(HSC)]的体外生产是再生医学的关键目标。然而,最近的努力,以产生功能齐全的组织特异性干细胞已经不足。缺陷的一个可能原因可能是用于表征基本脊椎动物胚胎学的模式生物(非洲爪蟾、斑马鱼、鸡)可能采用在人类中不保守的干细胞特化的分子机制,一个突出的例子是原始生殖细胞(PGCs)的特化。在许多模型中,种质不可逆地指定PGC;然而,它在人类中不保守,人类从称为生殖系感受态中胚层(GLCM)的组织产生PGC。GLCM在含有种质的生物体中不保守,甚至在小鼠中也不保守,但了解其发育潜力可以解锁其他干细胞类型的成功生产。GLCM最初是在美西螈的胚胎中发现的,后来在猪身上得到了证实,猪和人类一样是从一个扁平的圆盘胚胎发育而来的。总之,这些发现表明,GLCM是脊椎动物胚胎的保守的基础性状。此外,生殖细胞的不朽的性质表明,在GLCM规范中保留不朽;在这里,我们建议,已证明的多能性的GLCM占体干细胞类型中的不朽的保留以及。总结:最近的发现,生殖细胞和干细胞的规格可能不同的物种之间可能有重要的意义,再生医学和干细胞生物学的未来。
In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine. However, recent efforts to produce fully functional tissue-specific stem cells have fallen short. One possible cause of shortcomings may be that model organisms used to characterize basic vertebrate embryology (Xenopus, zebrafish, chick) may employ molecular mechanisms for stem cell specification that are not conserved in humans, a prominent example being the specification of primordial germ cells (PGCs). Germ plasm irreversibly specifies PGCs in many models; however, it is not conserved in humans, which produce PGCs from tissue termed germline-competent mesoderm (GLCM). GLCM is not conserved in organisms containing germ plasm, or even in mice, but understanding its developmental potential could unlock successful production of other stem cell types. GLCM was first discovered in embryos from the axolotl and its conservation has since been demonstrated in pigs, which develop from a flat-disc embryo like humans. Together these findings suggest that GLCM is a conserved basal trait of vertebrate embryos. Moreover, the immortal nature of germ cells suggests that immortality is retained during GLCM specification; here we suggest that the demonstrated pluripotency of GLCM accounts for retention of immortality in somatic stem cell types as well. Summary: Recent findings that germline and stem cell specification may differ between species may have important implications for regenerative medicine and the future of stem cell biology.
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