Stem cell fate and patterning in mammalian epidermis.

Recent studies highlight characteristics of epidermal stem cells that were not fully appreciated before. Stem cells are multipotential and signals exchanged with their neighbours help to regulate exit from the stem cell compartment and differentiation along specific lineages. Stem cells exhibit a high degree of spatial organisation, and cell clustering and motility contribute to the assembly and maintenance of the epidermis.     

Microprinted feeder cells guide embryonic stem cell fate

We introduce a non‐contact approach to microprint multiple types of feeder cells in a microarray format using immiscible aqueous solutions of two biopolymers. Droplets of cell suspension in the denser aqueous phase are printed on a substrate residing within a bath of the immersion aqueous phase. Due to their affinity to the denser phase, cells remain localized within the drops and adhere to regions of the substrate underneath the drops. We show the utility of this technology for creating duplex heterocellular stem cell niches by printing two different support cell types on a gel surface and overlaying them with mouse embryonic stem cells (mESCs). As desired, the type of printed support cell spatially direct the fate of overlaid mESCs. Interestingly, we found that interspaced mESCs colonies on differentiation‐inducing feeder cells show enhanced neuronal differentiation and give rise to dense networks of neurons. This cell printing technology provides unprecedented capabilities to efficiently identify the role of various feeder cells in guiding the fate of stem cells. Biotechnol. Bioeng. 2011;108: 2509–2516. © 2011 Wiley Periodicals, Inc.     

Epidermal stem cells: an update

The mammalian epidermis is a highly accessible tissue in which to study the properties of adult stem cells. Global gene expression profiling has revealed new markers and regulators of the stem cell compartment. Although stem cells have the potential to differentiate into multiple lineages, their progeny follow a more restricted number of lineages in undamaged epidermis as a result of local microenvironmental cues. The response of the epidermis to a particular signal depends on signal strength and duration. Recent advances in the field have led to elucidation of the mechanisms by which stem cells are maintained and the pathways that interact with Wnt signalling to specify lineage choice as cells leave the stem cell compartment. This work has also yielded new insights into skin tumour development.     

标记滞留细胞技术结合干细胞标记物检测小鼠子宫内膜干细胞

目的通过标记滞留细胞技术检测昆明小鼠子宫内膜干细胞的存在及其分布情况;观察P63和Musashi-1在不同周龄小鼠子宫内膜的表达以及两者与标记滞留细胞的关系,探讨P63和Musashi-1作为子宫内膜干细胞特异性标记物的可能性。方法出生3天雌性昆明小鼠皮下注射BrdU,分别在1w、2w、3w、4w、6w、8w和10w处死小鼠取其子宫。采用免疫组化法分别检测BrdU、P63和Musashi-1在各周龄小鼠子宫内膜的表达情况。结果标记后1w的小鼠,子宫内膜绝大部分的上皮和基质细胞都被BrdU标记。随着小鼠周龄的增加,子宫内膜BrdU阳性细胞百分率逐渐降低。至第8w时,仅在基质中有极少量的BrdU阳性细胞,主要位于基质与肌层交界处。早期小鼠子宫内膜组织中P63和Musashi-1阳性细胞数量较多,随着子宫内膜的逐渐发育成熟,P63和Musashi-1的表达逐渐减少,其表达规律及分布与标记滞留细胞基本一致。结论 (1)小鼠子宫内膜标记滞留细胞主要位于基质内膜与肌层交界处,这些细胞的分布与推测的子宫内膜干细胞的分布部位相符。(2)P63和Musashi-1是较特异的干细胞标记物。     

Altering cell fate: from thymus epithelium to skin stem cells

In a recent study in Nature, Bonfanti et?al. (2010) report that the skin microenvironment can convert thymic epithelial cells into skin stem cells. This finding suggests that somatic stem cells may have a broader potential for lineage switching than previously thought.     

Epigenetics: Judge,jury and executioner of stem cell fate

Emerging evidence is shedding light on a large and complex network of epigenetic modifications at play in human stem cells. This “epigenetic landscape” governs the fine-tuning and precision of gene expression programs that define the molecular basis of stem cell pluripotency, differentiation and reprogramming. This review will focus on recent progress in our understanding of the processes that govern this landscape in stem cells, such as histone modification, DNA methylation, alterations of chromatin structure due to chromatin remodeling and non-coding RNA activity. Further investigation into stem cell epigenetics promises to provide novel advances in the diagnosis and treatment of a wide array of human diseases.     

Epidermal cell patterning and differentiation throughout the apical-basal axis of the seedling

The idea of common pathways guiding different fates is an emerging concept in plant development, and epidermal cell-fate specification in Arabidopsis thaliana is an excellent example to illustrate it. In the root epidermis, both hair patterning and differentiation depend on a complex interaction between both negative (WER, TTG, GL3, EGL3, and GL2) and positive (CPC, TRY, and ETC1) regulators of hair cell fate. These regulators pattern and differentiate hairs through a bi-directional signalling mechanism. The same molecular components (WER, TTG, GL3, EGL3, and GL2) seem to be involved in the patterning of stomata in the embryonic stem. However, the possible role of CPC, TRY, and ETC1 on stomatal patterning and/or differentiation has not been studied, questioning whether they, and the underlying bi-directional mechanism, guide patterning formation and differentiation in the hypocotyl.     

皮肤表皮干细胞的研究进展

成体的皮肤一生都在不断的自我更新,其中的毛囊还是保证毛发进行生长-脱落周期循环的细胞组织学基础。存在于表皮内的干细胞维持了成体皮肤的自我平衡及毛发再生。表皮是由构体分子组成。每个构体分子包含毛皮脂单位（毛囊和皮脂腺）及其周围的毛囊间表皮。毛囊间表皮具有祖细胞,损伤时能自我更新;毛囊具有多能干细胞,在新毛发周期开始或者损伤时能够启动干细胞功能,为毛囊的生长或表皮的修复提供细胞来源。本文概述了当前对表皮干细胞的认识,着重阐明毛囊间表皮内有祖细胞的证据,毛囊间表皮干细胞在体外的自我更新能力,毛囊膨突部内干细胞的特征和一些相关基因的表达等。     

Evening the playing field: microenvironmental control over stem cell competition during fate programming

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Self-renewal, differentiation or death: regulation and manipulation of hematopoietic stem cell fate.

Hematopoietic stem cells (HSCs) are the rare cells from which all hematopoietic cells are derived. The absence of HSCs is not compatible with life because many essential cells, such as myeloid and erythroid cells, are short lived. The hematopoietic system is the first essential organ system that fails following cytotoxic treatments. It is the vulnerability of HSCs that prevents regeneration following treatment and thus long-term survival. Because HSCs have the capacity to regenerate a functional hematopoietic system, the manipulation of these cells in vitro holds many promises for gene-therapeutic and other applications; however, these are severely curtailed by current difficulties in maintaining and expanding HSCs in culture. This review focuses on recent approaches towards understanding how the HSC compartment is regulated in vivo and discusses how this knowledge might be applied to manipulating HSC numbers.     

Multifunctionality of PIWI proteins in control of germline stem cell fate

PIWI proteins interacting with specific type of small RNAs (piRNAs) repress transposable elements in animals. Besides, they have been shown to participate in various cellular processes: in the regulation of heterochromatin formation including telomere structures, in the control of translation and the cell cycle, and in DNA rearrangements. PIWI proteins were first identified by their roles in the self-renewal of germline stem cells. PIWI protein functions are not limited to gonadogenesis, but the role in determining the fate of stem cells is their specific feature conserved throughout the evolution of animals. Molecular mechanisms underlying these processes are far from being understood. This review focuses on the role of PIWI proteins in the control of maintenance and proliferation of germinal stem cells and its relation to the known function of PIWI in transposon repression.     

Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate

Lifelong neurogenesis in vertebrates relies on stem cells producing proliferation zones that contain neuronal precursors with distinct fates. Proliferation zones in the adult zebrafish brain are located in distinct regions along its entire anterior-posterior axis. We show a previously unappreciated degree of conservation of brain proliferation patterns among teleosts, suggestive of a teleost ground plan. Pulse chase labeling of proliferating populations reveals a centrifugal movement of cells away from their places of birth into the surrounding mantle zone. We observe tangential migration of cells born in the ventral telencephalon, but only a minor rostral migratory stream to the olfactory bulb. In contrast, the lateral telencephalic area, a domain considered homologous to the mammalian dentate gyrus, shows production of interneurons and migration as in mammals. After a 46-day chase, newborn highly mobile cells have moved into nuclear areas surrounding the proliferation zones. They often show HuC/D immunoreactivity but importantly also more specific neuronal identities as indicated by immunoreactivity for tyrosine hydroxylase, serotonin and parvalbumin. Application of a second proliferation marker allows us to recognize label-retaining, actively cycling cells that remain in the proliferation zones. The latter population meets two key criteria of neural stem cells: label retention and self renewal.