Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

Garza, Luis A.; Yang, Chao‐Chun; Zhao, Tailun; Blatt, Hanz; Lee, Michelle; He, Helen; Stanton, David C.; Carrasco, Lee; Spiegel, Jeffrey H.; Tobias, John W.; Cotsarelis, George

doi:10.1172/jci44478

Cited by 271 publications

(270 citation statements)

References 33 publications

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“…Skin was processed as described, 22,23 and 3-mm skin biopsy specimens were taken from areas of the occipital scalp, palms, soles, and corresponding dorsal positions from the hands and feet. Epidermis and dermis were separated using dispase II protease (SigmaAldrich, St. Louis, MO), as described in the literature, 22,24 and subjected for studies as below. Deidentified samples from paraffin-embedded blocks of diagnostic biopsy specimens for normal skins (volar and nonvolar), lichen simplex chronicus (LSC), and psoriasis were used for immunofluorescence analysis, also under Johns Hopkins University Institutional Review Board protocol approval (NA_00072381).…”

Section: Human Samplesmentioning

confidence: 99%

“…After removal of epidermis, papillary dermis of volar (palm and sole) and nonvolar (foreskin, scalp, hand, and foot) was placed and incubated for outgrowth of fibroblasts. 22,24 Keratinocytes were cultured in serum-reduced keratinocyte medium with defined growth factors (KGM-GOLD Bullet kit; Lonza, Walkersville, MD) and maintained at preconfluent state to prevent from differentiation until use. For all experiments, keratinocytes were used after two passages to eliminate contaminating cells.…”

Section: Krt9 Regulationmentioning

confidence: 99%

“…Previous studies provided evidence that differentiated keratinocytes secrete WNT5a and induce KRT1 in a b-cateninedependent promoting canonical cascade. 22 Also, separate studies have shown that WNT5a from volar fibroblasts induce ectopic KRT9 expression in nonvolar keratinocytes, 20,21 although it was further proposed that WNT5a acts as a proximal-distal signal and induces KRT9 in a noncanonical cascade by inhibiting b-catenin activity. 7,21 Because WNT5a expression gradually increases during keratinocyte differentiation ( Figure 3B), we speculated instead that the canonical WNT signaling pathway might promote KRT9 expression in both autocrine and paracrine contexts.…”

Section: B-catenin Promotes Krt9 Expressionmentioning

confidence: 99%

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To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease

Kim¹,

Hossain²,

Nieves³

et al. 2016

The American Journal of Pathology

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Despite similar components, the heterogeneity of skin characteristics across the human body is enormous. It is classically believed that site-specific fibroblasts in the dermis control postnatal skin identity by modulating the behavior of the surface-overlying keratinocytes in the epidermis. To begin testing this hypothesis, we characterized the gene expression differences between volar (ventral; palmoplantar) and nonvolar (dorsal) human skin. We show that KERATIN 9 (KRT9) is the most uniquely enriched transcript in volar skin, consistent with its etiology in genetic diseases of the palms and soles. In addition, ectopic KRT9 expression is selectively activated by volar fibroblasts. However, KRT9 expression occurs in the absence of all fibroblasts, although not to the maximal levels induced by fibroblasts. Through gain-of-function and loss-of-function experiments, we demonstrate that the mechanism is through overlapping paracrine or autocrine canonical WNTeb-catenin signaling in each respective context. Finally, as an in vivo example of ectopic expression of KRT9 independent of volar fibroblasts, we demonstrate that in the human skin disease lichen simplex chronicus, WNT5a and KRT9 are robustly activated outside of volar sites. These results highlight the complexities of site-specific gene expression and its disruption in skin disease. Site-specific epidermal differentiation programs define the heterogeneity of skin identity across the human body. It is generally believed that positional skin identity is regulated by epithelial (keratinocytes) and mesenchymal (fibroblasts) interactions. 1e5 Indeed, three-dimensional skin equivalent models and transplantation experiments show that epidermal stratification during the keratinocyte differentiation program is remarkably disrupted in the absence of fibroblasts, 2,4,5 demonstrating that epidermal development and homeostasis are regulated by extrinsic factors released by fibroblasts. Such interactions have been further clarified through an analysis of the differential localization of epidermal keratins in distinct epidermal layers and body sites. Volar (palmoplantar) skin is characterized by thick epidermal layers, less pigmentation, and lack of hair. In addition to these features, cytoskeleton KERATIN (KRT) 9 6 has been thought to be almost exclusively localized to volar keratinocytes, 1,6e9 indicating that KRT9 can be a unique marker for volar skin. To date, many clinical studies have reported that KRT9 mutations cause epidermolytic palmoplantar keratoderma, characterized by compensatory thickened epidermal layers in the palms and soles. 10 Conditional deletion of Krt9 in a murine model demonstrated that Krt9 is responsible for maintaining mechanical integrity and terminal differentiation of volar skin.

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Section: Human Samplesmentioning

confidence: 99%

Section: Krt9 Regulationmentioning

confidence: 99%

Section: B-catenin Promotes Krt9 Expressionmentioning

confidence: 99%

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To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease

Kim¹,

Hossain²,

Nieves³

et al. 2016

The American Journal of Pathology

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View full text Add to dashboard Cite

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“…As mentioned earlier, platelets are absolutely essential for hair growth and platelet rich plasma preparations are potentially useful in prevention of hair loss [3][4][5][6][7][8][9][10][11]. Despite the facts that the platelets count in AGA patients was at normal range with 238.16 ± 59.70 × 10 3 platelet/µL, but it was lower than that in control group with 267.79 ± 68.23 × 10 3 platelet/µL (P value < 0.01).…”

Section: Resultsmentioning

confidence: 99%

“…This kind of baldness is described as progressive loss in pigmented terminal hair on the scalp concurrent with predominant onset in puberty upon increase in sexual hormones [4][5][6]. Histological investigations indicated that elevated androgenic hormones cause marked decrease in hair follicles sizes, probably by decreasing hair progenitor cells [7]. Despite the uncertainty regarding the involvement of androgens in AGA especially in women, no progression of baldness was seen in pre-puberty period.…”

Section: Introductionmentioning

confidence: 99%

Androgenetic Alopecia: A Chronic or Pubertal Onset Disease Retarded by Blood Donation

Dayer

Dehghani

Daer³

et al. 2017

Zahedan J Res Med Sci

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Background: Androgenetic alopecia is the main cause of hair loss and common baldness that affects psychological more than physiological aspects of people's lives. Studies have shown that this multi factorial disorder is initiated by androgens secretion in pubertal period, minerals limitations, autoimmunity, mental stress, genetic predisposition and some alterations in hematological factors. Objectives: The aim of this study was to evaluate the involvement of hematologic parameters in this disease using a case control study design. Methods: In this case-controlled study, two groups each of 80 individuals with androgenetic alopecia were voluntarily included in the study based on their medical histories and clinical examinations and subjected to blood tests for routine hematological parameters. The results were then compared and analyzed using SPSS version 16.0.

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Clinicopathologic Characteristics and Response to Treatment of Persistent Chemotherapy-Induced Alopecia in Breast Cancer Survivors

Bhoyrul

Asfour

Lutz³

et al. 2021

JAMA Dermatol

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IMPORTANCE Alopecia induced by classic chemotherapy affects up to 65% of patients and is usually reversible. However, there are increasing reports of persistent chemotherapy-induced alopecia (pCIA), especially for patients treated with taxane-containing chemotherapy regimens.OBJECTIVE To analyze the clinicopathologic characteristics and response to treatment of patients with pCIA after chemotherapy for breast cancer.DESIGN, SETTING, AND PARTICIPANTS In this case series, a retrospective evaluation was performed of patients with a diagnosis of pCIA after chemotherapy for breast cancer in 4 specialist hair clinics from November 1, 2011, to February 29, 2020.MAIN OUTCOMES AND MEASURES Clinical, trichoscopic, and histopathologic characteristics and treatment outcomes were analyzed. For patients who presented with diffuse alopecia or diffuse rarefaction of hair over the midfrontal scalp with widening of the central part line and preservation of the frontal hairline, the Sinclair scale (grades 1-5, where 1 indicates normal hair density and 5 indicates the most severe stage of hair loss, with little or no hair in the centroparietal region) was used to assess severity. RESULTSOne hundred patients (99 women [99%]; mean age at presentation, 54.0 years [range, 29.0-74.1 years]) were included. Most patients had diffuse nonscarring alopecia (n = 39), female pattern hair loss (n = 55), or male pattern hair loss (n = 6). Six patients developed cicatricial alopecia. Taxane-containing regimens were used for most patients (92 [92%]) and were associated with more severe alopecia than regimens that did not contain taxanes (median Sinclair grade, 4 [IQR, 3-5] vs 2 [IQR, 2-2.5]; P < .001). A total of 76 of 86 patients (88%) had trichoscopic signs indistinguishable from those of androgenetic alopecia. Of 18 patients who had biopsies, 14 had androgenetic alopecia-like features, 2 had cicatricial alopecia, and 2 had features of both. Both topical and oral minoxidil, sometimes combined with antiandrogen therapy, were associated with an improvement in hair density (median Sinclair grade, 4 [IQR, 3-5] before treatment vs 3 [IQR, 2-4] after treatment; P < .001).CONCLUSIONS AND RELEVANCE This case series outlines previously unreported features of pCIA in patients with breast cancer, including a trichoscopic description. Cosmetically significant regrowth was achieved for a significant proportion of patients with topical or systemic treatments, suggesting that pCIA may be at least partly reversible.

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Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

Cited by 271 publications

References 33 publications

To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease

To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease

Androgenetic Alopecia: A Chronic or Pubertal Onset Disease Retarded by Blood Donation

Clinicopathologic Characteristics and Response to Treatment of Persistent Chemotherapy-Induced Alopecia in Breast Cancer Survivors

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