Natural selection at the cellular level: insights from male germ cell differentiation.
Natural selection at the cellular level: insights from male germ cell differentiation.
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DOI：
10.1038/s41418-021-00812-0
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发表时间：
2021-07
影响因子：
12.4
通讯作者：
Laird DJ
中科院分区：
文献类型：
--
作者：
Nguyen DH;Laird DJ
Waddington’s concept of differentiation as an epigenetic landscape provides an enduring metaphor visualizing the options faced by stem and progenitor cells. However, increasing understanding of cellular heterogeneity poses new questions about the identities and behaviors of the cells beginning this process. We now recognize a greater diversity of initial states for individual progenitor cells, which may affect their trajectories and disrupt progress entirely. Here, we consider how developmental selection occurs when heterogeneity in differentiating progenitors produces divergent cellular outcomes of survival versus elimination. Heterogeneity is a fundamental property of biological systems. Individual cell properties like location or cell cycle can yield vastly different behaviors, and single cell analysis offers deeper characterization of transcriptional and genetic diversity. Heterogeneity in progenitors can wield lasting impacts on the composition of lineages. Variable Myc expression in epiblast cells generates selection for Myc-high populations [1] and similar enrichment occurs based on differential Hippo signaling [2]. Heterogeneous expression of P53 [3] or mTOR [4] forms the basis for clonal expansion in hematopoietic stem cells and early mouse embryos. In these examples, differentiation from heterogeneous progenitors involves cell competition and active elimination based on fitness. Importantly, competitive states are heritable across cell division, evoking principles similar to Darwinian selection. Moreover, evidence of developmental failure and selection challenges the notion that differentiation follows a robust and stable trajectory, especially at the individual cell level.The germline is a fascinating context for investigating the consequences of heterogeneity on differentiation and cell fate. As fetal germ cells establish the gametes, their population dynamics can greatly influence inheritance. The conflict between diversity and orderly differentiation looms centrally over germline development. In mouse embryos, germ cells undertake an epic journey, from specification through sex differentiation, replete with opportunities for heterogeneity to develop and be assessed. Notably, an excess of germ cells is produced and then pruned by programmed cell death [5]. This occurs across diverse species regardless of sex, suggesting that differential fitness and elimination are critical.
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