这是17年Trends in Cell Biology上发表的一篇关于肠道细胞发育层级（hierarchy）与干细胞可塑性（plasticity）的综述，通讯是滨州大学的Christopher J. Lengner
1、通过lineage-tracing实验发现的Lgr5干细胞和造血系统中的祖细胞功能类似
Box 1. Stem Cell Dynamics in the Hematopoietic System
（关于造血干细胞的一些介绍，这里特别指出造血干细胞移植后HSCs相对于正常生理条件下的HSCs很可能发生了改变，肠道研究中也要注意这一点）
HSCs serve as a paradigm for the study of adult stem cells. HSCs are defined as cells with the ability to self-renew and the potential to give rise to all hematopoietic lineages. HSCs are a heterogeneous population with LT and ST subsets. LT HSCs versus ST HSCs are distinguished by their ability to support hematopoiesis post-transplantation into recipient mice for the lifetime (LT) or a few months (ST); however, these definitions are arbitrary and subject to change as the field progresses. ST HSCs give rise to multipotent progenitor cells (MPPs) that have the potential to give rise to all hematopoietic lineages but lack LT self-renewal ability, as evidenced by their limited ability to support hematopoiesis post-transplantation. MPPs can further give rise to common myeloid progenitors (CMPs), which produce mega- erythroid progenitors (MEPs) and granulocyte–macrophage progenitors (GMPs). The latter two are the resources of mature megakaryocytes, erythrocytes, granulocytes, and macrophages. On the axis of immune lineages, MPPs can give rise to common lymphoid progenitors (CLPs) and the latter further produce T, B, and NK cells. This ‘clonal succession’ model in which a very small number of LT HSCs at the apex of the hematopoietic pedigree generate the entire hematopoietic system at any given time has been dominant in the field for decades. However, this model is based on the transplantation assay, a nonphysiological condition that can be considered highly stressful and relies on a cell’s ability to survive in the circulation and home to the bone marrow. Thus, the transplantation assay may better represent a post-injury regenerative scenario rather than a readout of homeostatic HSC function. Whether basal (or native) hematopoiesis behaviors follow this model has recently been challenged.
Recent observations indicate that under basal conditions LT HSCs rarely divide over the lifetime; and mice can tolerate loss of LT HSCs for up to 6 months without showing any lineage bias. These observations suggest that LT HSCs function only as a back-up or reserve subpopulation under basal conditions on shorter-term (6 months) timeframes. Taking an alternative approach by employing retrotransposition as a means to uniquely barcode individual cells and their lineage, researchers demonstrated that a pool of long-lived progenitors, rather than classically defined LT HSCs, is the main driver of basal hematopoiesis during most of adulthood. Our understanding of stem cell activity in the intestinal epithelium is derived largely from in vivo lineage tracing in native (non-transplanted) tissue; however, in vitro organoid culture and transplantation assays have recently been pioneered in this tissue. These assays may be more analogous to the transplantation assays used to define the HSC compartment. We should therefore be cognizant of the limitations of each assay and may find value in comparing results from transplantation versus native stem cell activity in both the blood and the intestine.
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