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A family business: stem cell progeny join the niche to regulate homeostasis

Nature Reviews Molecular Cell Biology volume 13, pages 103–114 (2012)Cite this article

Subjects

Key Points

  • Stem cells reside in specialized microenvironments, known as niches. Cellular components of the niche have important roles in regulating various stem cell behaviours, including activation, dormancy, differentiation and migration.

  • Traditionally, stem cell niches are thought to be composed of heterologous cell types derived from different lineages. Surprisingly, however, increasing evidence from both invertebrate and vertebrate stem cell systems shows that stem cell progeny themselves can also be important niche components and/or regulators of stem cell activity.

  • In the Drosophila melanogaster male germline, progeny of the somatic cyst stem cells can contribute to their niche, which is called the 'hub'. Although this contribution may be low during steady state, certain fly mutations have been found to cause the somatic cyst stem cells to adopt a hub cell fate.

  • In the mouse hair follicle, stem cells reside in the outermost layer of the follicle stem cell niche, which is located in an anatomical region known as the bulge. As these stem cells progress along their lineages to produce the hair and its channel, some terminally differentiated progeny end up back in the bulge, where they locate within the inner layer and function to maintain stem cell quiescence in the niche.

  • In the intestine, fast-cycling intestinal stem cells are located at the bottom of the crypt and are interspersed by terminally differentiated progeny called Paneth cells. Reduction of Paneth cell numbers is accompanied by a concomitant reduction in the stem cell population, suggesting a possible role of Paneth cells in regulating stem cell self-renewal.

  • In the adult haematopoietic system, most haematopoietic stem cells (HSCs) reside in the bone marrow. In this niche, regulatory T cells protect the HSCs from immune attack by making the niche an immune-privileged site. The mobilization and migration of HSCs also appears to be regulated by at least one additional HSC downstream lineage: macrophages.

Abstract

Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

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Figure 1: Overview of adult stem cells.
Figure 2: CySCs contribute to 'hub' maintenance.
Figure 3: The HFSC niche: a dynamic interplay between HFSC progeny and dermal components.
Figure 4: ISCs generate Paneth cells that promote stem cell proliferation at the base of the intestinal crypt.
Figure 5: The HSC niche: a rich and complex environment.

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Acknowledgements

We thank B. Keyes, T. Chen and M. Genander for critical readings and comments of the manuscript. Y.-C.H. was a Starr Stem Cell Scholars postdoctoral fellow and is now supported by a New York Stem Cell Foundation–Druckenmiller fellowship. E.F. is a Howard Hughes Medical Institute Investigator. This work is supported by a grant from the US National Institutes of Health (R01-AR050452).

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  1. Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, 10065, New York, USA

    Ya-Chieh Hsu & Elaine Fuchs

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Correspondence to Elaine Fuchs.

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Basement membrane

A sheet-like structure that is composed of extracellular matrix and separates the cavity and surfaces of an organ.

Cancer stem cells

Long-term self-renewing cells within a tumour that are responsible for initiating the cancer and propagating it. The term does not reflect the origin of these cells or their molecular similarities to normal stem cells. Rather, these cells are tumour-initiating cells and can execute a differentiation programme, but it is an aberrant one.

Bulge

A protruding structure of the hair follicle in which hair follicle and melanocyte stem cells reside.

Integrins

A family of cell adhesion receptors that mediate either cell–cell interactions or cell–extracellular matrix interactions. Integrins are heterodimers with two distinct subunits, which are known as the α-subunit and the β-subunit.

Hair shaft

A terminally differentiated structure that protrudes out from the skin surface as a hair.

Transient amplifying progeny

A special population of stem cell progeny responsible for the bulk of tissue growth. Transient amplifying cells are larger in quantity and are capable of massive expansion and proliferation within in a short time. However, they can only undergo a finite number of divisions.

Crypt

A moat-like tubular invagination of the intestinal epithelium. Crypts contain intestinal stem cells and Paneth cells.

Villi

Finger-like structures that project into the lumen of the intestine. Villi contain the absorptive enterocytes and mucus-secreting goblet cells. These cells live for a few days before they die and are shed from the intestinal epithelium.

Myeloid

A lineage containing macrophages, monocytes, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes and dendritic cells.

Lymphoid

A lineage containing all of the T cells, B cells and natural killer cells.

Myelofibrosis

A disease in which fibrous scars accumulate in the bone marrow cavity.

Non-myelinating Schwann cells

Schwann cells are the glia cells of the peripheral nerve system. Non-myelinating Schwann cells lack a myelin sheath. They are often found to wrap around axons with a smaller diameter and are important for the survival and function of neurons

Endosteal lining

A thin layer of connective tissue that lines the medullary cavity of a bone.

Mesenchymal stem cells

(MSCs). Multipotent stem cells capable of giving rise to a wide range of mesenchymal cells, including adipocytes, chondrocytes and osteoblasts.

Myelodysplasia

A group of disorders in which the bone marrow does not function normally and insufficient numbers of blood cells are produced.

Syngeneic

When donors are genetically identical or at least immunologically compatible with recipients.

Allogeneic

When donors are from the same species but are genetically different from recipients.

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Hsu, YC., Fuchs, E. A family business: stem cell progeny join the niche to regulate homeostasis. Nat Rev Mol Cell Biol 13, 103–114 (2012). https://doi.org/10.1038/nrm3272

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