Poblet E, Jimenez F, Godinez JM et al.The immunohistochemical expression of CD34 in human hair follicles: a comparative study with the bulge marker CK15. Clin Exp Dermatol 31:807-812

University of Castilla-La Mancha, Ciudad Real, Castille-La Mancha, Spain
Clinical and Experimental Dermatology (Impact Factor: 1.09). 12/2006; 31(6):807-12. DOI: 10.1111/j.1365-2230.2006.02255.x
Source: PubMed
ABSTRACT
Anti-CD34 antibodies label the bulge region of mouse hair follicles. However, in human hair follicles, CD34 immunoreactivity is found in the outer root sheath below the bulge zone. The immunohistochemical staining of CD34 in catagen and telogen follicles has not been evaluated.
To characterize the expression of CD34 immunoreactivity at different stages of the hair cycle in human terminal hair follicles, and to compare the immunostaining pattern of CD34 with that of CK15, used here as a marker of the bulge region.
Serial vertical sections of human hair follicles in anagen, catagen and telogen phases were immunostained with anti-CD34 (QBEnd 10) and anti-CK15 (LHK15 and C8/144B) antibodies. Double-labelling immunofluorescence was also performed.
The catagen and telogen follicles studied did not show CD34 immunoreactivity in the outer root sheath. The location of CD34 and CK15 immunoreactivity in anagen follicles reveals a different staining pattern: CD34-positive cells are located in the outer root sheath below the attachment zone of the arrector pili muscle, whereas CK15-positive cells are located in the outer root sheath above the attachment zone of the arrector pili muscle.
Only anagen human hair follicles show CD34 immunoreactivity. CD34 and CK15 recognize different types of cells or cells at different stages of differentiation.

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The immunohistochemical expression of CD34 in human hair
follicles: a comparative study with the bulge marker CK15
E. Poblet, F. Jime
´
nez,* J.M. Godı
´
nez,† A. Pascual-Martı
´
n and A. Izeta‡
Department of Pathology, and Research Unit, Hospital General Universitario de Albacete, Universidad de Castilla La Mancha, Albacete, Spain; *Clı
´
nica
Dr Jime
´
nez Acosta, Las Palmas de Gran Canaria, Spain; and Fundacio
´
n Inbiomed, San Sebastia
´
n, Spain
Summary Background. Anti-CD34 antibodies label the bulge region of mouse hair follicles.
However, in human hair follicles, CD34 immunoreactivity is found in the outer root
sheath below the bulge zone. The immunohistochemical staining of CD34 in catagen
and telogen follicles has not been evaluated.
Aims: To characterize the expression of CD34 immunoreactivity at different stages of
the hair cycle in human terminal hair follicles, and to compare the immunostaining
pattern of CD34 with that of CK15, used here as a marker of the bulge region.
Method. Serial vertical sections of human hair follicles in anagen, catagen and tel-
ogen phases were immunostained with anti-CD34 (QBEnd 10) and anti-CK15 (LHK15
and C8 144B) antibodies. Double-labelling immunofluorescence was also performed.
Results. The catagen and telogen follicles studied did not show CD34 immuno-
reactivity in the outer root sheath. The location of CD34 and CK15 immunoreactivity
in anagen follicles reveals a different staining pattern: CD34-positive cells are located in
the outer root sheath below the attachment zone of the arrector pili muscle, whereas
CK15-positive cells are located in the outer root sheath above the attachment zone of
the arrector pili muscle.
Conclusions. Only anagen human hair follicles show CD34 immunoreactivity. CD34
and CK15 recognize different types of cells or cells at different stages of differentiation.
Introduction
CD34 is a 110-kDa, heavily glycosylated, transmem-
brane protein encoded by a gene located on chromo-
some 1q and expressed on haematopoietic stem cells,
vascular endothelial cells, embryonic fibroblasts, and
fibroblast-like dendritic cells in connective tissues.
1
In
the skin, CD34 is expressed in a variety of mesenchymal-
derived cells such as vascular endothelial cells, dermal
dendritic spindle-shaped cells, and perifollicular cells.
2
In diagnostic pathology, CD34 is used as a marker of
vascular and spindle cell tumours, such as Kaposi’s
sarcoma and dermatofibrosarcoma protuberans.
To our knowledge, the hair follicle is the only human
structure in which the expression of CD34 in epithelial
cells has been reported.
3
CD34-positive cells were
initially described in the outermost cell layer of the
external root sheath of anagen human hair follicles, in a
segment below the attachment of the arrector pili
muscle and above the matrix cells.
3
A recent study has
confirmed that in human follicles, CD34 expression at
the external root sheath does not include the bulge area,
which is currently considered the niche for epithelial
stem cells.
4
In contrast, there is a significantly different
CD34 immunostaining pattern on mouse hair follicles,
in which CD34-positive cells are found at a higher level
of the follicle, specifically at the bulge region.
5
More-
over, these CD34-positive bulge cells in murine follicles
identify keratinocytes with typical characteristics of
Correspondence: Dr Francisco Jime
´
nez, Angel Guimera
´
, 2, 35003 Las
Palmas de Gran Canaria, Spain.
E-mail: fjimenez@clinicadelpelo.com
Conflict of interest: none declared.
Accepted for publication 18 July 2006
Experimental dermatology Original article doi: 10.1111/j.1365-2230.2006.02255.x
2006 The Author(s)
Journal compilation 2006 Blackwell Publishing Ltd, Clinical and Experimental Dermatology, 31, 807–812
807
Page 1
stem cells: they are slow-cycling keratinocytes with the
capacity to form large colonies.
In the microscopic anatomy of the follicle, the bulge
region can be recognized as a prominent protuberance
below the sebaceous gland in vertical sections of murine
and human foetus specimens stained with haematoxy-
lin and eosin. In contrast, in adult human follicles, the
bulge region is barely prominent and is identified only
by its correspondence with the insertion of the arrector
pili muscle. Recent evidence suggests important struc-
tural and or biological differences between the human
and the mouse outer root sheath, including the bulge
zone.
4
One of the most reliable immunohistochemical
markers of the bulge region of human hair follicles
in formalin-fixed, paraffin wax-embedded sections is
cytokeratin (CK) 15. The antibodies used for the
detection of CK15 are derived from two different
clones, C8 144B
6
and LHK15.
7
In human hair folli-
cles, the C8 144B antibody, originally raised against
the carboxy-terminal peptide of the T-lymphocyte
protein, CD8, delineates the bulge region in anagen,
telogen and catagen follicles.
6
Likewise, in formalin-
fixed tissues, the LHK15 antibody, raised against a
peptide derived from the last 17 amino acids of the
CK15 polypeptide, delineates the isthmus area and a
small segment of the outer root sheath located above
the hair bulb.
8
However, when used in frozen sections,
the antibody LHK15 appears to have a more extensive
immunostaining pattern.
7
The aim of this study was to further characterize
the expression of CD34 immunoreactivity in human
terminal hair follicles not only in anagen human
follicles, but also in catagen and telogen hair follicles.
In order to precisely define the location of the CD34
immunoreactivity we used vertical serial sections of
the entire length of the hair follicles and compared the
microscopic location of CD34 and CK15 immuno-
reactivity, the latter used here as a marker of the
bulge region.
Materials and methods
Tissue samples
Normal human scalp samples from 15 surgical pathol-
ogy specimens were selected from specimens received at
the Department of Pathology, Albacete University Gen-
eral Hospital. All specimens were fixed using buffered
formalin and embedded in paraffin wax. About 120 hair
follicles in different stages of the hair cycle (most of them
in anagen phase, and others in catagen and telogen
phases) could be examined. Serial sections were cut
following a standard protocol to examine the same hair
follicle stained with haematoxylin and eosin, CK15, and
CD34. The protocol was as follows: sections were 3–
5 lm thick, and three consecutive single sections were
retrieved and mounted on separate slides for the three
different stains.
In addition, 27 follicular units harvested from human
scalp were obtained from five different donors. The
follicular units were harvested using a 1-mm circular
punch. The manipulation of these follicular units was
very meticulous when it came to making the paraffin-
wax blocks and the microtome cutting, as the goal was
to obtain parallel sections that included all the length of
the hair follicles. In order to obtain consecutive sections
of the same hair follicles, the same protocol described
above was used. The only difference was that the series
consisted of four slides, because two different anti-CK15
antibodies (C8 144B and LHK15) were used.
Only the hair follicles that could be visualized along
their complete length were submitted for immunohisto-
chemical analysis. These included 96 hair follicles in
anagen, 4 in catagen and 15 in telogen phase.
Immunohistochemistry
Two anti-CK15 antibodies (clone LHK15; Novocastra,
Newcastle, UK, and clone C8 144B; Dako, Glostrup
Denmark), and one anti-CD34 antibody (clone QBEnd
10; Dako) were used in our study.
The immunohistochemical method used for the
C8 144B antibody was as described by Lyle et al.
8
Briefly, the paraffin-wax sections were first dewaxed,
and then steamed for 15 min in citrate buffer
(10 mmol l sodium citrate pH 6.77) at 85 C prior to
incubating overnight at 4 C with the anti-CD8 anti-
body (dilution 1 : 40). The avidin–biotin-complex tech-
nique was used for development, and diaminobenzidine
for visualization, followed by haematoxylin counter-
stain.
For the immunohistochemical staining with LHK15
and QBEnd 10, the samples were dewaxed and
steamed for 40 min in citrate buffer pH 7 at 95 C.
The antibody LHK15 was diluted to 1 : 80 and the
QBEnd was diluted to 1 : 50. The incubation time with
the primary antibodies was 30 min. The secondary
antibodies used were those included in the kit (REAL
detection system; Dako), with an incubation time of
15 min. Human hair follicles were immunostained
using the standard avidin–streptavidin staining meth-
od, and an automatic staining apparatus (Cytomation
autostainer; Dako).
2006 The Author(s)
808 Journal compilation 2006 Blackwell Publishing Ltd, Clinical and Experimental Dermatology, 31, 807–812
CD34 in human hair follicles. E. Poblet et al.
Page 2
Normal structures that should not be labelled with
these markers (i.e. endothelium for CK15, and epidermis
for CD34) served as internal negative controls.
Immunofluorescence double labelling
This technique was used to better delineate the location
of the expression of CD34 and CK15 by comparing in
the same section the areas stained with both antibodies.
Sections were dewaxed and then steamed for 40 min in
citrate buffer (pH 7) at 95 C for antigen retrieval. The
first antibody to be applied was the anti-CD34 QBend10
(1 : 50, 30 min at room temperature), followed by a
biotinylated secondary antibody, and by fluorescein-
labelled streptavidin (Cy2, dilution 1 : 100, goat
antirabbit; Amersham Biosciences). Slides were then
incubated with nonimmune calf serum for 30 min in
order to reduce nonspecific binding, and then with the
anti-LHK15 antibody, dilution 1 : 80, for 30 min at
room temperature. Finally, rodamine antimouse anti-
body was applied (Cy3, dilution 1 : 100; Amersham
Biosciences). The buffer used to rinse the sections
between the different incubations was a Tris-buffered
saline Tween buffer, diluted 1 : 10 with deionized
water. The sections were imaged using a Leica DM
IRE2 confocal microscope. The laser used to observe the
fluorescence was the Leica TCS SP2.
Results
CD34 immunoreactivity
In the typical anagen human follicle, CD34 immuno-
reactivity was detected at the most peripheral layer of
the outer root sheath, in the transient portion of the
follicle, below the isthmus and above the matrix cells
(Figs 1 and 2). The anti-CD34 antibody stained the
epithelial cells located at the outermost layer of the
external root sheath (Fig. 1b). CD34 immunoreactivity
was not detected in catagen or in telogen hair follicles
(Figs 3 and 4). As expected, other skin structures that
stained with the CD34 antibody were the endothelial
cells, dendritic spindle-shaped dermal cells and perifol-
licular spindle-shaped cells.
Cytokeratin 15 immunoreactivity
In typical anagen follicles, CK15 was expressed in the
outermost cell layer of the external root sheath, at the
level of the isthmus. Specifically, the CK15 immuno-
staining extended from the entrance of the sebaceous
gland duct down to the insertion site of the arrector pili
muscle (Fig. 2). This CK15 staining was maintained
throughout the different phases of the hair follicle cycle
(Figs 3 and 4). The two anti-CK15 antibodies used in
this study, LHK15 and C8 144B, showed the same
immunostaining pattern. A few CK15-positive cells
were also detected in the external root sheath just
above the bulb. Other skin structures that stained with
both CK15 antibodies were basal cells from the epider-
mis and secretory cells from eccrine glands.
(a)
(b)
Figure 1 Longitudinal section of human scalp. Left, CD34
expression in spindle-shaped dermal cells, endothelial cells and
perifollicular spindle-shaped cells, and in epithelial cells of the
outer root sheath. Right, high-power image showing CD34-posit-
ive epithelial cells in the most external layer of the outer root
sheath. CD34 immunostaining, original magnification (a) · 25;
(b) · 200.
2006 The Author(s)
Journal compilation 2006 Blackwell Publishing Ltd, Clinical and Experimental Dermatology, 31, 807–812
809
CD34 in human hair follicles. E. Poblet et al.
Page 3
Figure 2 Serial vertical sections of a human terminal anagen hair follicle, stained with (from left) haematoxylin and eosin, anti-CD34, and
two anti-CK15 antibodies (original magnification · 25). Sections are consecutive cuts of the same hair follicle. All the nonepithelial,
perifollicular, CD34-positive cells have been artificially removed in order to show the epithelial area of staining clearly. CD34 immuno-
reactivity was detected in the external root sheath, at the level of the inferior portion of the follicle, below the isthmus and above the matrix
cells. CK15 was expressed at the level of the isthmus, between the sebaceous-gland duct and down to the insertion site of the arrector pili
muscle (the bulge zone). Both anti-CK15 antibodies (LHK15 and C8 144B) showed similar immunoreactivity. Comparing the CD34 and
CK15 immunoreactivity reveals a different immunostaining pattern: CD34 stains below the bulge zone and CK15 stains at the isthmus
level. INF, infundibulum; IST, isthmus; AP, arrector pili. The bulge region (black circle), by definition, corresponds to the attachment site of
the AP muscle.
Figure 3 Comparison of CD34 and CK15
immunostaining (original magnification
· 40) in human catagen hair follicles.
CD34 immunoreactivity was not detected
in the residual outer root sheath. CK15
was strongly expressed by epithelial cells of
the isthmus.
Figure 4 Serial vertical sections of a telo-
gen hair follicle stained with (from left)
haematoxylin and eosin, CD34 and CK15
(original magnification · 40). Intense
positive CK15 immunostaining is clearly
seen surrounding the telogen club. CD34
immunoreactivity was not detected in
telogen follicles.
2006 The Author(s)
810 Journal compilation 2006 Blackwell Publishing Ltd, Clinical and Experimental Dermatology, 31, 807–812
CD34 in human hair follicles. E. Poblet et al.
Page 4
Comparison of CD34 and CK15 immunoreactivity
It may be deduced from consecutive sections of the same
hair follicle that the areas that stained with the anti-
CD34 antibody and the anti-CK15 antibodies were
completely different. A double immunofluorescence
study showed that the segment of the follicle positive
for CD34 was located almost in continuity with, but
below the zone that stained with CK15 (Fig. 5).
Discussion
We examined the immunohistochemical pattern of
CD34 in human hair follicles at different phases of the
cycle. In anagen follicles, we demonstrated CD34
immunoreactivity in epithelial cells of the outer root
sheath below the bulge zone, an observation already
reported in our previous work.
3
However, we extended
our observations to catagen and telogen follicles,
showing that CD34 immunostaining tends to disappear
in catagen and is absent in telogen follicles.
Comparing the immunostaining pattern of CD34 with
the immunostaining pattern of CK15, used in our study
as a bulge marker of human follicles, we confirmed that
CD34-positive cells are located below the bulge zone.
The results of the immunostaining pattern with two
different antibodies anti-CK15 concur with previous
reports,
6,8
and show that CK15-positive cells are mainly
found at the most peripheral layer of the outer root
sheath at the level of the isthmus, specifically between
the entrance of the sebaceous duct and the insertion site
of the arrector pili muscle, although a less intense
staining can be observed in suprabulbar cells. This
CK15 immunostaining at the isthmus level was main-
tained in catagen and telogen follicles, where an intense
CK15 staining could be seen surrounding the telogen
club. The different CD34 and CK15 immunostaining
patterns indicate that these two markers recognize
different types of cells or cells at different stages of
differentiation. Lyle et al.
6
showed that the CK15-
positive bulge cells possess the proliferative behaviour
and biochemical properties of epithelial stem cells.
However, the significance of the CD34 immunoreactiv-
ity in epithelial cells of the lower external root sheath in
human hair follicles is unknown. The fact that human
catagen and telogen follicles lose their CD34 expression
could indicate that CD34 is not a lineage-specific
antigen, but may be related to certain functions in
anagen or growing cells. A possible role of CD34 in
cytoadhesion and signalling related to differentiation
and proliferation has been suggested.
9
Based on this
adhesive property, we speculate that the CD34 antigen
might contribute to increasing the adhesion of the
external root sheath to the perifollicular stroma in
anagen follicles. However, it is also possible that the
disappearance of the CD34 immunoreactivity in cat-
agen and telogen follicles might be the result of the
destruction by apoptosis that takes place in the transient
portion of the follicle, with the subsequent loss of CD34
expression by those cells.
Although CD34 identifies a subset of bulge keratino-
cytes with characteristics of stem cells in murine
follicles, this is not the case in human follicles. Ohyama
et al.
4
have recently characterized the gene-expression
profile and cell-surface markers of the bulge region of
human follicles, confirming that CD34 expression is low
Figure 5 Double-immunofluorescence study of a vertical section of
an anagen hair follicle. The area of the follicle shown in this pic-
ture corresponds to the lower portion of the isthmus (CK15+,
stained green) and the upper portion of the transient segment of
the hair follicle (CD34+, stained red). The areas stained with both
markers appear to be clearly different and do not overlap. Original
magnification · 400.
2006 The Author(s)
Journal compilation 2006 Blackwell Publishing Ltd, Clinical and Experimental Dermatology, 31, 807–812
811
CD34 in human hair follicles. E. Poblet et al.
Page 5
or absent in human bulge cells with stem cell-charac-
teristics. These authors have shown that human bulge
cells with stem cell properties have a CD200
hi
CD34
lo
surface phenotype. Nevertheless, the possibility that the
CD34-positive cells of the lower outer root sheath of
human follicles still retain some clonogenic capacity
cannot, according to previous studies on clonal analysis,
be excluded. The location of the CD34 immunoreactivity
in human follicles concurs with the area in whcih
Rochat et al.
10
found the highest clonogenic capacity. In
this classic experiment of clonal analysis, these inves-
tigators examined the in vitro proliferative behaviour of
dissociated keratinocytes from microdissected portions
of human hair follicles, and found that an area of the
hair follicle below the bulge, but above the bulb, in the
lower outer root sheath, contained the highest percent-
age of clonogenicity. Other evidence indicating that
these CD34-positive cells of the outer root sheath retain
significant proliferative capacity is their potential to give
rise to a neoplasm known as trichilemmoma.
3
In summary, in this study we have clarified the
expression of CD34 in hair follicles from human scalp.
We have confirmed that CD34 is expressed in epithelial
cells of the external root sheath only in anagen follicles,
and is not expressed in catagen or telogen hair follicles.
The location of CD34 and CK15 immunostaining is
different and they do not overlap, suggesting that they
recognize different types of cells or cells at different
stages of differentiation.
Acknowledgements
This work has been supported by grant FIS PI03-1364.
The authors express their appreciation to Dr de Cabo
and Dr Atienzar for their thoughtful review of the
manuscript, to Ms Sanchis for her collaboration with
the confocal laser microscopy technique, and to
Ms Prieto for technical assistance. JMG is supported by
a fellowship from Balague Center S.A.
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Page 6
  • Source
    • "Epithelial cell adhesion molecule (EpCAM), when detected via Ber-EP4 antibody, is considered to be a useful marker of the human telogen SHG [66, 67]. The SHG is reportedly negative for K15 (LHK15 but not C8/144b, see Supporting Information) and K19 [67] as well as for CD34 (CD34 IR is not sustained in the catagen or telogen human HF [44, 68] (Fig. 2)) but is partially positive for CD200 [46]. The SHG is responsible for de novo hair matrix formation during anagen development and thus it could be posited that it must contain critical epithelial "
    [Show abstract] [Hide abstract] ABSTRACT: Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain and renew the continuously cycling hair follicle (HF), supply cells that produce the keratinized hair shaft and aid in the reepithelialization of injured skin. Therefore, their study is biologically and clinically important, from alopecia to carcinogenesis and regenerative medicine. However, human eHFSCs remain ill defined compared to their murine counterparts, and it is unclear which murine eHFSC markers really apply to the human HF. We address this by reviewing current concepts on human eHFSC biology, their immediate progeny and their molecular markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4. After delineating how human eHFSCs may be selectively targeted experimentally, we close by defining as yet unmet key challenges in human eHFSC research. The ultimate goal is to transfer emerging concepts from murine epithelial stem cell biology to human HF physiology and pathology.
    Full-text · Article · May 2014 · BioEssays
  • Source
    • "MSC-epithelial transdifferentiation has been demonstrated in several stud- ies52535455. CD34 + progenitors of keratinocytes in the skin are well documented565758. We previously found CD34 + keratocytes that coexpressed the corneal epithelial marker CK3, indicating the potential for transdifferentiation from mesenchyme to epithelial lineages [59]. "
    [Show abstract] [Hide abstract] ABSTRACT: The corneal stroma is being increasingly recognized as a repository for stem cells. Like the limbal and endothelial niches, stromal stem cells often reside in the peripheral cornea and limbus. These peripheral and limbal corneal stromal cells (PLCSC) are known to produce mesenchymal stem cells in vitro. Recently, a common corneal stromal and epithelial progenitor has been hinted at. This study aims to examine the stem cell potential of corneal stromal cells and to investigate their epithelial transdifferentiation ability. PLCSC were grown in traditional Dulbecco's modified Eagle's medium (DMEM)-based keratocyte culture medium and an M199-based medium and analysed for a profile of cell surface markers using flow cytometry and differentiated into mesenchymal phenotypes analysed by qPCR and histological staining. PLCSC in M199 were subsequently divided into subpopulations based on CD34 and CD105 expression using fluorescent activated cell sorting (FACS). Subpopulations were characterized by marker profile and mesenchymal differentiation ability. Both whole PLCSC and subpopulations were also cultured for epithelial transdifferentiation. Cells cultured in M199 demonstrated a more stem-like cell surface marker profile and the keratocyte marker CD34 was retained for several passages but absent in cells cultured in DMEM. Cells cultured in M199 also exhibited a greater mesenchymal differentiation potential, compared with DMEM. PLCSC could be divided into CD34+CD105+, CD34-CD105+ and CD34-CD105- subpopulations, of which CD34+CD105+ cells were the most stem-like with regard to marker expression and mesenchymal differentiation potential. Subpopulations of PLCSC exhibited differing abilities to transdifferentiate into epithelial phenotypes. Cells that were initially CD34+CD105+ showed greatest differentiation potential producing CK3+ and CK19+ cells, and expressed a range of both epithelial progenitor (HES1, FRZB1, DCT, SOD2, ABCG2, CDH1, KRT19) and terminally differentiated (DSG3, KRT3, KRT12, KRT24) genes. Culture medium has a significant effect on the phenotype and differentiation capacity of PLCSC. The stroma contains a heterogeneous cell population in which we have identified CD34+ cells as a stem cell population with a capacity for mesenchymal and epithelial differentiation.
    Full-text · Article · Jun 2013 · Stem Cell Research & Therapy
  • Source
    • "Although Lhx2 expression appears to be mandatory regarding the induction of hair growth from a quiescent telogen state, so far no specific epithelial subpopulation has been linked to it. In wild type, a CD49f expressing progenitor typically found in the basal layer of the epidermis [21], [22] is most predominant, followed by CD34 expressing progenitors that are most abundant at the root sheet level of hair follicles below the bulge region [23], [44], [45], [46], [47] (Fig. 1). In addition, a population highly (++) positive for CD49f can typically be distinguished from a population with intermediate (+) positivity. "
    [Show abstract] [Hide abstract] ABSTRACT: Hair cycling is a prime example of stem cell dependent tissue regeneration and replenishment, and its regulatory mechanisms remain poorly understood. In the present study, we evaluated the effect of a blockage in terminal keratinocytic lineage differentiation in the Foxn1(-/-) nude phenotype on the epithelial progeny. Most notably we found a constitutive upregulation of LIM homeobox protein 2 (Lhx2), a marker gene of epithelial stem cellness indispensible for hair cycle progression. However, histological evidence along with an erratic, acyclic rise of otherwise suppressed CyclinD1 levels along with several key markers of keratinocyte lineage differentiation indicate a frustrated expansion of epithelial stem cell niches in skin. In addition, CD49f/CD34/CD200-based profiling demonstrated highly significant shifts in subpopulations of epithelial progeny. Intriguingly this appeared to include the expansion of Oct4+ stem cells in dermal fractions of skin isolates in the Foxn1 knock-out opposed to wild type. Overall our findings indicate that the Foxn1(-/-) phenotype has a strong impact on epithelial progeny and thus offers a promising model to study maintenance and regulation of stem cell niches within skin not feasible in other in vitro or in vivo models.
    Full-text · Article · May 2013 · PLoS ONE
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