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Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments

Nature Reviews Molecular Cell Biology volume 16, pages 299–309 (2015)Cite this article

Subjects

Key Points

  • The concept of a strictly hierarchical model of tissue regeneration in which a uniform pool of stem cells that continuously regenerates somatic tissues has recently been re-evaluated.

  • In the haematopoietic system, stem cells with distinct differentiation preferences generate progeny in a lineage-biased manner. New data suggest that there is sustained production of specific cell types from highly specialized long-term progenitors, overturning traditional views.

  • The skin epithelium, which includes the interfollicular epidermis, the hair follicle and the sebaceous gland, contains heterogeneous pools of stem cells that maintain their discrete compartments during homeostasis. In transplantation assays or in response to injury, these stem cells are no longer restricted in their lineage choice.

  • Specific niches that surround the different pools of stem cells define the identities and behaviours of the stem cells.

  • Under normal conditions, the intestinal epithelium is primarily maintained by crypt base columnar (CBC) stem cells. Following injury, or in the absence of CBC cells, other cells can maintain and repair the intestine. Reserve or quiescent stem cells (qISCs; also known as +4 cells) are thought to be important for repair, but progenitors and differentiated cells may also revert to function as stem cells.

  • The identity and characteristics of stem cell types and the mechanisms of their differential regulation through intrinsic and extrinsic signals remain to be determined.

Abstract

Somatic stem cells replenish many tissues throughout life to repair damage and to maintain tissue homeostasis. Stem cell function is frequently described as following a hierarchical model in which a single master cell undergoes self-renewal and differentiation into multiple cell types and is responsible for most regenerative activity. However, recent data from studies on blood, skin and intestinal epithelium all point to the concomitant action of multiple types of stem cells with distinct everyday roles. Under stress conditions such as acute injury, the surprising developmental flexibility of these stem cells enables them to adapt to diverse roles and to acquire different regeneration capabilities. This paradigm shift raises many new questions about the developmental origins, inter-relationships and molecular regulation of these multiple stem cell types.

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Figure 1: Stem cell models for the haematopoietic system.
Figure 2: Heterogeneity of skin epithelial stem cells.
Figure 3: Overview of the intestinal stem cell system.

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Acknowledgements

Research in the Goodell laboratory is supported by the US National Institutes of Health (NIH) (grants DK092883 and CA183252), the Edward P. Evans Foundation, and the Samuel Waxman Cancer Research Foundation. Research in the Nguyen laboratory is supported by R01AR059122. Work in the Shroyer laboratory is supported by the US NIH grants DK092456, DK092306, CA1428260 and DK103117.

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  1. Stem Cells and Regenerative Medicine Center and Departments of Pediatrics, Molecular and Cellular Biology, and Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Margaret A. Goodell, Hoang Nguyen & Noah Shroyer

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  1. Margaret A. Goodell
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  2. Hoang Nguyen
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  3. Noah Shroyer
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Correspondence to Margaret A. Goodell.

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Glossary

Quiescence

The state of being inactive. This usually implies limited mitotic activity and is sometimes referred to as dormancy.

Niches

The local environments in which stem cells reside. Niches are thought to regulate stem cell activity through various types of interaction.

CrePR

A Cre recombinase fused with a truncated progesterone receptor that translocates into the nucleus when the receptor binds to the progesterone antagonist RU486.

CreER

A Cre recombinase fused with an oestrogen receptor that translocates into the nucleus when the receptor binds to the oestrogen antagonist tamoxifen. When it translocates to the nucleus, the Cre recombinase is activated and removes the sequences preceding the reporter gene, allowing expression of the reporter.

Quiescent label-retaining cells

Cells that are labelled with a pulse of 5-bromo-2-deoxyuridine (BrdU) and that retain the BrdU label when followed for a certain amount of time.

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Goodell, M., Nguyen, H. & Shroyer, N. Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments. Nat Rev Mol Cell Biol 16, 299–309 (2015). https://doi.org/10.1038/nrm3980

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