NG2 Proteoglycan Expression in Mouse Skin: Altered Postnatal Skin Development in the NG2 Null Mouse

In early postnatal mouse skin, the NG2 proteoglycan is expressed in the subcutis, the dermis, the outer root sheath of hair follicles, and the basal keratinocyte layer of the epidermis. With further development, NG2 is most prominently expressed by stem cells in the hair follicle bulge region, as also observed in adult human skin. During telogen and anagen phases of the adult hair cycle, NG2 is also found in stem cell populations that reside in dermal papillae and the outer root sheaths of hair follicles. Ablation of NG2 produces alterations in both the epidermis and subcutis layers of neonatal skin. Compared with wild type, the NG2 null epidermis does not achieve its full thickness due to reduced proliferation of basal keratinocytes that serve as the stem cell population in this layer. Thickening of the subcutis is also delayed in NG2 null skin due to deficiencies in the adipocyte population.

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Migration of Melanoblasts into the Developing Murine Hair Follicle Is Accompanied by Transient c-Kit Expression

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540205000602 ◽

2002 ◽

Vol 50 (6) ◽

pp. 751-766 ◽

Cited By ~ 78

Author(s):

Eva M. J. Peters ◽

Desmond J. Tobin ◽

Natasha Botchkareva ◽

Marcus Maurer ◽

Ralf Paus

Keyword(s):

Stem Cell ◽

Hair Follicle ◽

Stem Cell Factor ◽

Mouse Skin ◽

Dermal Papilla ◽

Hair Follicles ◽

Cell Populations ◽

Outer Root Sheath ◽

Hair Bulb ◽

Root Sheath

Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 0–4 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-mela-nogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearance. During the subsequent stages (5 and 6), increasingly dendritic c-Kit-IR cells successively invaded the hair bulb, while S100-IR gradually disappeared from these cells. Towards the completion of hair follicle morphogenesis (stages 7 and 8), several distinct follicular melanocytic cell populations could be defined and consisted broadly of (a) undifferentiated, non-pigmented c-Kit-negative melanoblasts in the outer root sheath and bulge and (b) highly differentiated melanocytes adjacent to the hair follicle dermal papilla above Auber's line. Widespread epithelial SCF-IR was seen throughout hair follicle morphogenesis. These findings suggest that melanoblasts express c-Kit as a prerequisite for migration into the SCF-supplying hair follicle epithelium. In addition, differentiated c-Kit-IR melanocytes target the bulb, while non-c-Kit-IR melanoblasts invade the outer root sheath and bulge in fully developed hair follicles.

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The Adipose-derived Stem Cell: Looking Back and Looking Ahead

Molecular Biology of the Cell ◽

10.1091/mbc.e09-07-0589 ◽

2010 ◽

Vol 21 (11) ◽

pp. 1783-1787 ◽

Cited By ~ 217

Author(s):

Patricia A. Zuk

Keyword(s):

Stem Cell ◽

Historical Perspective ◽

Es Cells ◽

Adult Stem Cell ◽

Stem Cell Population ◽

Cell Populations ◽

Stem Cell Populations ◽

New Applications ◽

Adipose Derived Stem Cell ◽

Looking Back

In 2002, researchers at UCLA published a manuscript in Molecular Biology of the Cell describing a novel adult stem cell population isolated from adipose tissue—the adipose-derived stem cell (ASC). Since that time, the ASC has gone on to be one of the most popular adult stem cell populations currently being used in the stem cell field. With multilineage mesodermal potential and possible ectodermal and endodermal potentials also, the ASC could conceivably be an alternate to pluripotent ES cells in both the lab and in the clinic. In this retrospective article, a historical perspective on the ASC is given together with exciting new applications for the stem cell being considered today.

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Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells

Blood ◽

10.1182/blood.v84.8.2422.bloodjournal8482422 ◽

1994 ◽

Vol 84 (8) ◽

pp. 2422-2430 ◽

Cited By ~ 8

Author(s):

FC Zeigler ◽

BD Bennett ◽

CT Jordan ◽

SD Spencer ◽

S Baumhueter ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Tyrosine Kinase ◽

Hematopoietic Stem Cell ◽

Receptor Tyrosine Kinase ◽

Lymphoid Cells ◽

Stem Cell Population ◽

Cell Populations ◽

Hematopoietic Stem ◽

Stem Cell Populations

The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic stem cell population and is considered to play a potential role in the developmental fate of the stem cell. Using antibodies derived against the extracellular domain of the receptor, we show that stem cells from both murine fetal liver and bone marrow can express flk-2/flt-3. However, in both these tissues, there are stem cell populations that do not express the receptor. Cell cycle analysis shows that stem cells that do not express the receptor have a greater percentage of the population in G0 when compared with the flk-2/flt-3- positive population. Development of agonist antibodies to the receptor shows a proliferative role for the receptor in stem cell populations. Stimulation with an agonist antibody gives rise to an expansion of both myeloid and lymphoid cells and this effect is enhanced by the addition of kit ligand. These studies serve to further illustrate the importance of the flk-2/flt-3 receptor in the regulation of the hematopoietic stem cell.

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CCN2 modulates hair follicle cycling in mice

Molecular Biology of the Cell ◽

10.1091/mbc.e13-08-0472 ◽

2013 ◽

Vol 24 (24) ◽

pp. 3939-3944 ◽

Cited By ~ 13

Author(s):

Shangxi Liu ◽

Andrew Leask

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hair Follicle ◽

Cell Activity ◽

Adult Life ◽

Tissue Growth ◽

Hair Follicles ◽

Outer Root Sheath ◽

Root Sheath ◽

Dermal Papillae

It is critical to understand how stem cell activity is regulated during regeneration. Hair follicles constitute an important model for organ regeneration because, throughout adult life, they undergo cyclical regeneration. Hair follicle stem cells—epithelial cells located in the follicle bulge—are activated by periodic β-catenin activity, which is regulated not only by epithelial-derived Wnt, but also, through as-yet-undefined mechanisms, the surrounding dermal microenvironment. The matricellular protein connective tissue growth factor (CCN2) is secreted into the microenvironment and acts as a multifunctional signaling modifier. In adult skin, CCN2 is largely absent but is unexpectedly restricted to the dermal papillae and outer root sheath. Deletion of CCN2 in dermal papillae and the outer root sheath results in a shortened telogen-phase length and elevated number of hair follicles. Recombinant CCN2 causes decreased β-catenin stability in keratinocytes. In vivo, loss of CCN2 results in elevated numbers of K15-positive epidermal stem cells that possess elevated β-catenin levels and β-catenin–dependent reporter gene expression. These results indicate that CCN2 expression by dermal papillae cells is a physiologically relevant suppressor of hair follicle formation by destabilization of β-catenin and suggest that CCN2 normally acts to maintain stem cell quiescence.

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Isolation and Characterization of a Fetal-Maternal Microchimeric Stem Cell Population in Maternal Hair Follicles Long after Parturition

Stem Cell Reviews and Reports ◽

10.1007/s12015-019-09885-4 ◽

2019 ◽

Vol 15 (4) ◽

pp. 519-529 ◽

Cited By ~ 2

Author(s):

Cosmin Andrei Cismaru ◽

Olga Soritau ◽

Ancuta - Maria Jurj ◽

Raduly Lajos ◽

Bogdan Pop ◽

...

Keyword(s):

Stem Cell ◽

Cell Population ◽

Hair Follicles ◽

Stem Cell Population ◽

Isolation And Characterization

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Hair follicles serve as local reservoirs of skin mast cell precursors

Blood ◽

10.1182/blood-2003-02-0449 ◽

2003 ◽

Vol 102 (5) ◽

pp. 1654-1660 ◽

Cited By ~ 58

Author(s):

Tadashi Kumamoto ◽

David Shalhevet ◽

Hiroyuki Matsue ◽

Mark E. Mummert ◽

Brant R. Ward ◽

...

Keyword(s):

Mast Cell ◽

Stem Cell ◽

Mast Cells ◽

Local Development ◽

Mouse Skin ◽

Γδ T Cells ◽

Hair Follicles ◽

Tissue Type ◽

Adult Mice ◽

Leukocyte Populations

AbstractSeveral leukocyte populations normally reside in mouse skin, including Langerhans cells and γδ T cells in the epidermis and macrophage and mast cells in the dermis. Interestingly, these skin resident leukocytes are frequently identified within or around hair follicles (HFs), which are known to contain stem cell populations that can generate the epidermal architecture or give rise to the melanocyte lineage. Thus, we reasoned that HFs might serve as a local reservoir of the resident leukocyte populations in the skin. When vibrissal follicles of adult mice were cultured in the presence of stem cell factor (SCF), interleukin 3 (IL-3), IL-7, granulocyte-macrophage colony-stimulating factor, and Flt3 ligand, CD45+/lineage–/c-kit+/FcϵRI+ cells became detectable on the outgrowing fibroblasts in 10 days and expanded progressively thereafter. These HF-derived leukocytes showed characteristic features of connective tissue-type mast cells, including proliferative responsiveness to SCF, metachromatic granules, mRNA expression for mast cell proteases-1, -4, -5, and -6, and histamine release on ligation of surface IgE or stimulation with substance P or compound 48/80. These results, together with our findings that HFs contain c-kit+ cells and produce SCF mRNA and protein, suggest that HFs provide a unique microenvironment for local development of mast cells.

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The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers

Biomolecules ◽

10.3390/biom11020154 ◽

2021 ◽

Vol 11 (2) ◽

pp. 154

Author(s):

Hanluo Li ◽

Federica Francesca Masieri ◽

Marie Schneider ◽

Alexander Bartella ◽

Sebastian Gaus ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hair Follicle ◽

Cell Populations ◽

Stem Cell Markers ◽

Outer Root Sheath ◽

Root Sheath ◽

Gene And Protein Expression ◽

Stem Cell Populations

Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells.

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The Implications of Small Stem Cell Niche Sizes and the Distribution of Fitness Effects of New Mutations in Aging and Tumorigenesis

10.1101/032813 ◽

2015 ◽

Cited By ~ 2

Author(s):

Vincent L. Cannataro ◽

Scott A. McKinley ◽

Colette M. St. Mary

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Simulation Analysis ◽

Somatic Tissue ◽

Stem Cell Population ◽

Cell Populations ◽

Regulatory Regime ◽

Fitness Effects ◽

Cell Niche ◽

Stem Cell Populations

Somatic tissue evolves over a vertebrate's lifetime due to the accumulation of mutations in stem cell populations. Mutations may alter cellular fitness and contribute to tumorigenesis or aging. The distribution of mutational effects within somatic cells is not known. Given the unique regulatory regime of somatic cell division we hypothesize that mutational effects in somatic tissue fall into a different framework than whole organisms; one in which there are more mutations of large effect. Through simulation analysis we investigate the fit of tumor incidence curves generated using exponential and power law Distributions of Fitness Effects (DFE) to known tumorigenesis incidence. Modeling considerations include the architecture of stem cell populations, i.e., a large number of very small populations, and mutations that do and do not fix neutrally in the stem cell niche. We find that the typically quantified DFE in whole organisms is sufficient to explain tumorigenesis incidence. Further, due to the effects of small stem cell population sizes, i.e., strong genetic drift, deleterious mutations are predicted to accumulate, resulting in reduced tissue maintenance. Thus, despite there being a large number of stem cells throughout the intestine, its compartmental architecture leads to significant aging, a prime example of Muller's Ratchet.

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Tfap2b specifies an embryonic melanocyte stem cell population that retains adult multi-fate potential

10.1101/2021.06.18.448859 ◽

2021 ◽

Author(s):

Alessandro Brombin ◽

Daniel J. Simpson ◽

Jana Travnickova ◽

Hannah R. Brunsdon ◽

Zhiqiang Zeng ◽

...

Keyword(s):

Stem Cell ◽

Neural Crest ◽

Pigment Cell ◽

Cell Types ◽

Lineage Tracing ◽

Stem Cell Population ◽

Cell Of Origin ◽

Lineage Markers ◽

Melanocyte Stem Cell ◽

Stem Cell Populations

Melanocytes, our pigment producing cells, originate from neural crest-derived progenitors during embryogenesis and from multiple stem cell niches in adult tissues. Although pigmentation traits are known risk-factors for melanoma, we lack lineage markers with which to identify melanocyte stem cell populations and study their function. Here, by combining live-imaging, scRNA-seq and chemical-genetics in zebrafish, we identify the transcription factor Tfap2b as a functional marker for the melanocyte stem cell (MSC) population that resides at the dorsal root ganglia site. Tfap2b is required for only a few late-stage embryonic melanocytes, and instead is essential for MSC-dependent melanocyte regeneration. Our lineage-tracing data reveal that tfap2b-expressing MSCs have multi-fate potential, and are the cell-of-origin for a discrete number of embryonic melanocytes, large patches of adult melanocytes, and two other pigment cell types; iridophores and xanthophores. Hence, Tfap2b confers MSC identity, and thereby distinguishes MSCs from other neural crest and pigment cell lineages.

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Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury

Molecular Biology of the Cell ◽

10.1091/mbc.e11-01-0035 ◽

2011 ◽

Vol 22 (14) ◽

pp. 2532-2540 ◽

Cited By ~ 18

Author(s):

Kerry-Ann Nakrieko ◽

Alena Rudkouskaya ◽

Timothy S. Irvine ◽

Sudhir J. A. D'souza ◽

Lina Dagnino

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hair Follicle ◽

Hair Follicles ◽

Stem Cell Population ◽

Epidermal Surface ◽

Hair Follicle Stem Cells ◽

Integrin Linked Kinase ◽

Hair Follicle Growth ◽

Follicle Stem Cells

Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15–expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

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