Lord Tessa, Oatley Jon M
Center for Reproductive BiologySchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Center for Reproductive BiologySchool of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
Reproduction. 2017 Aug;154(2):R55-R64. doi: 10.1530/REP-17-0034.
Spermatogonial stem cells (SSCs) and progenitor spermatogonia encompass the undifferentiated spermatogonial pool in mammalian testes. In rodents, this population is comprised of A, A and chains of 4-16 A spermatogonia. Although traditional models propose that the entire A pool represents SSCs, and formation of an A syncytium symbolizes irreversible entry to a progenitor state destined for differentiation; recent models have emerged that suggest that the A pool is heterogeneous, and A/A can fragment to produce new SSCs. In this review, we explore evidence from the literature for these differing models representing SSC dynamics, including the traditional 'A' and more recently formed 'fragmentation' models. Further, based on findings using a fluorescent reporter transgene () that reflects expression of the SSC-specific transcription factor 'inhibitor of DNA binding 4' (), we propose a revised version of the traditional model in which SSCs are a subset of the A population; the ID4-eGFP bright cells (SSC). From the SSC pool, other A and A cohorts arise that are ID4-eGFP dim. Although the SSC possess a transcriptome profile that reflects a self-renewing state, the transcriptome of the ID4-eGFP dim population resembles that of cells in transition (SSCtransitory) to a progenitor state. Accordingly, at the next mitotic division, these SSC are likely to join the progenitor pool and have lost stem cell capacity. This model supports the concept of a linear relationship between spermatogonial chain length and propensity for differentiation, while leaving open the possibility that the SSC (some A and potentially some A spermatogonia), may contribute to the self-renewing pool rather than transition to a progenitor state in response to perturbations of steady-state conditions.
精原干细胞（SSCs）和祖代精原细胞构成了哺乳动物睾丸中未分化的精原细胞库。在啮齿动物中，这一群体由A单倍体、A成对细胞以及4 - 16个A链精原细胞组成。尽管传统模型认为整个A类细胞群都代表精原干细胞，并且A类细胞形成合胞体象征着不可逆地进入注定分化的祖代状态；但最近出现的模型表明，A类细胞群是异质的，A单倍体/A成对细胞可以分裂产生新的精原干细胞。在本综述中，我们探讨了文献中支持这些代表精原干细胞动态变化的不同模型的证据，包括传统的“A类细胞”模型和最近形成的“分裂”模型。此外，基于使用荧光报告转基因（）的研究结果，该转基因反映了精原干细胞特异性转录因子“DNA结合抑制因子4”（）的表达，我们提出了传统模型的修订版，其中精原干细胞是A类细胞群体中的一个子集；即ID4-eGFP高表达细胞（精原干细胞）。从精原干细胞库中产生了其他ID4-eGFP低表达的A单倍体和A成对细胞群体。尽管精原干细胞拥有反映自我更新状态的转录组图谱，但ID4-eGFP低表达群体的转录组类似于向祖代状态转变的细胞（过渡性精原干细胞）。因此，在下一次有丝分裂时，这些精原干细胞可能会加入祖代细胞库并失去干细胞能力。该模型支持精原细胞链长度与分化倾向之间存在线性关系的概念，同时也保留了这样一种可能性，即精原干细胞（一些A单倍体以及可能一些A链精原细胞）可能会在稳态条件受到干扰时，继续留在自我更新库中，而不是过渡到祖代状态。
