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Genetic reporter analysis reveals an expandable reservoir of OCT4+ cells in adult skin.

Limbourg A, Schnabel S, Lozanovski VJ, Napp LC, Ha TC, Maetzig T, Bauersachs J, Naim HY, Schambach A, Limbourg FP - Cell Regen (Lond) (2014)

Bottom Line: However, analysis of Oct4 expression is confounded by Oct4 pseudogenes or non-pluripotency-related isoforms.Interestingly, skin wounding or non-traumatic hair removal robustly expanded the GFP(+) epidermal cell pool not only locally, but also in uninjured skin areas, demonstrating the existence of a systemic response.Thus, the epithelial stem cell niche of the hair follicle harbors an expandable pool of Oct4+ stem cells, which might be useful for therapeutic cell transfer or facilitated reprogramming.

View Article: PubMed Central - PubMed

Affiliation: Research Group Regenerative Agents, Hannover, Germany ; REBIRTH Cluster of Excellence, Hannover, Germany ; Integrated Research Center Transplantation (IFB-Tx), Hannover, Germany ; Department of Plastic, Hand and Reconstructive Surgery, Hannover, Germany.

ABSTRACT
The transcription factor Oct4 (Pou5f1) is a critical regulator of pluripotency in embryonic and induced pluripotent stem cells. Therefore, Oct4 expression might identify somatic stem cell populations with inherent multipotent potential or a propensity for facilitated reprogramming. However, analysis of Oct4 expression is confounded by Oct4 pseudogenes or non-pluripotency-related isoforms. Systematic analysis of a transgenic Oct4-EGFP reporter mouse identified testis and skin as two principle sources of Oct4 (+) cells in postnatal mice. While the prevalence of GFP(+) cells in testis rapidly declined with age, the skin-resident GFP(+) population expanded in a cyclical fashion. These cells were identified as epidermal stem cells dwelling in the stem cell niche of the hair follicle, which endogenously expressed all principle reprogramming factors at low levels. Interestingly, skin wounding or non-traumatic hair removal robustly expanded the GFP(+) epidermal cell pool not only locally, but also in uninjured skin areas, demonstrating the existence of a systemic response. Thus, the epithelial stem cell niche of the hair follicle harbors an expandable pool of Oct4+ stem cells, which might be useful for therapeutic cell transfer or facilitated reprogramming.

No MeSH data available.


Related in: MedlinePlus

Dynamic expansion of GFP+cells in skin. (A) Localized punch injury to dorsal skin. Left, FACS count of GFP+ cells from dorsal (dors) and abdominal (abd) skin. n = 14-28. P vs. same side basal (0). Right, box blot of epidermal GFP+ cells from wound area (W) vs remote (R) dorsal skin at d3. n = 13. (B) Box plot of epidermal GFP+ cells by FACS after non-traumatic skin depilation, age 12–14 wks, n = 9-28. P vs. basal (d0). (C) Immunostaining against smooth muscle–actin (red) and GFP (green) in flank skin after dorsal depilation, DAPI (blue). Scale bar: 20 um, magnification: 400 (upper panel), 640 (lower panel). GFP- gated cells from skin. CD34+ ITGα6hi and CD34+ ITGα6lo populations are indicated. (H).
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Fig2: Dynamic expansion of GFP+cells in skin. (A) Localized punch injury to dorsal skin. Left, FACS count of GFP+ cells from dorsal (dors) and abdominal (abd) skin. n = 14-28. P vs. same side basal (0). Right, box blot of epidermal GFP+ cells from wound area (W) vs remote (R) dorsal skin at d3. n = 13. (B) Box plot of epidermal GFP+ cells by FACS after non-traumatic skin depilation, age 12–14 wks, n = 9-28. P vs. basal (d0). (C) Immunostaining against smooth muscle–actin (red) and GFP (green) in flank skin after dorsal depilation, DAPI (blue). Scale bar: 20 um, magnification: 400 (upper panel), 640 (lower panel). GFP- gated cells from skin. CD34+ ITGα6hi and CD34+ ITGα6lo populations are indicated. (H).

Mentions: The cyclic and synchronized expansion of GFP+ skin cells observed during postnatal maturation suggested regulation by external cues. To test this hypothesis we analyzed the behavior of GFP + cells following dorsal skin wounding by punch biopsy in adult mice. Follwing wounding, there was a rapid and transient increase in GFP+ cells in dorsal skin. However, this response was not limited to areas of injury, but also occurred in remote dorsal skin areas, and even in abdominal skin (Figure 2A). This suggests a systemic signal controlling GFP+ cell expansion in response to injury. Furthermore, non-traumatic hair removal by depilation, which stimulates the hair follicle without skin injury, induced a comparable expansion of stem cells throughout the skin (Figure 2B, and data not shown). Following depilation, GFP+ cells were also detected outside the bulge region along the structures provided by smooth muscle cells, suggesting mobilization (Figure 2C).Figure 2


Genetic reporter analysis reveals an expandable reservoir of OCT4+ cells in adult skin.

Limbourg A, Schnabel S, Lozanovski VJ, Napp LC, Ha TC, Maetzig T, Bauersachs J, Naim HY, Schambach A, Limbourg FP - Cell Regen (Lond) (2014)

Dynamic expansion of GFP+cells in skin. (A) Localized punch injury to dorsal skin. Left, FACS count of GFP+ cells from dorsal (dors) and abdominal (abd) skin. n = 14-28. P vs. same side basal (0). Right, box blot of epidermal GFP+ cells from wound area (W) vs remote (R) dorsal skin at d3. n = 13. (B) Box plot of epidermal GFP+ cells by FACS after non-traumatic skin depilation, age 12–14 wks, n = 9-28. P vs. basal (d0). (C) Immunostaining against smooth muscle–actin (red) and GFP (green) in flank skin after dorsal depilation, DAPI (blue). Scale bar: 20 um, magnification: 400 (upper panel), 640 (lower panel). GFP- gated cells from skin. CD34+ ITGα6hi and CD34+ ITGα6lo populations are indicated. (H).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230759&req=5

Fig2: Dynamic expansion of GFP+cells in skin. (A) Localized punch injury to dorsal skin. Left, FACS count of GFP+ cells from dorsal (dors) and abdominal (abd) skin. n = 14-28. P vs. same side basal (0). Right, box blot of epidermal GFP+ cells from wound area (W) vs remote (R) dorsal skin at d3. n = 13. (B) Box plot of epidermal GFP+ cells by FACS after non-traumatic skin depilation, age 12–14 wks, n = 9-28. P vs. basal (d0). (C) Immunostaining against smooth muscle–actin (red) and GFP (green) in flank skin after dorsal depilation, DAPI (blue). Scale bar: 20 um, magnification: 400 (upper panel), 640 (lower panel). GFP- gated cells from skin. CD34+ ITGα6hi and CD34+ ITGα6lo populations are indicated. (H).
Mentions: The cyclic and synchronized expansion of GFP+ skin cells observed during postnatal maturation suggested regulation by external cues. To test this hypothesis we analyzed the behavior of GFP + cells following dorsal skin wounding by punch biopsy in adult mice. Follwing wounding, there was a rapid and transient increase in GFP+ cells in dorsal skin. However, this response was not limited to areas of injury, but also occurred in remote dorsal skin areas, and even in abdominal skin (Figure 2A). This suggests a systemic signal controlling GFP+ cell expansion in response to injury. Furthermore, non-traumatic hair removal by depilation, which stimulates the hair follicle without skin injury, induced a comparable expansion of stem cells throughout the skin (Figure 2B, and data not shown). Following depilation, GFP+ cells were also detected outside the bulge region along the structures provided by smooth muscle cells, suggesting mobilization (Figure 2C).Figure 2

Bottom Line: However, analysis of Oct4 expression is confounded by Oct4 pseudogenes or non-pluripotency-related isoforms.Interestingly, skin wounding or non-traumatic hair removal robustly expanded the GFP(+) epidermal cell pool not only locally, but also in uninjured skin areas, demonstrating the existence of a systemic response.Thus, the epithelial stem cell niche of the hair follicle harbors an expandable pool of Oct4+ stem cells, which might be useful for therapeutic cell transfer or facilitated reprogramming.

View Article: PubMed Central - PubMed

Affiliation: Research Group Regenerative Agents, Hannover, Germany ; REBIRTH Cluster of Excellence, Hannover, Germany ; Integrated Research Center Transplantation (IFB-Tx), Hannover, Germany ; Department of Plastic, Hand and Reconstructive Surgery, Hannover, Germany.

ABSTRACT
The transcription factor Oct4 (Pou5f1) is a critical regulator of pluripotency in embryonic and induced pluripotent stem cells. Therefore, Oct4 expression might identify somatic stem cell populations with inherent multipotent potential or a propensity for facilitated reprogramming. However, analysis of Oct4 expression is confounded by Oct4 pseudogenes or non-pluripotency-related isoforms. Systematic analysis of a transgenic Oct4-EGFP reporter mouse identified testis and skin as two principle sources of Oct4 (+) cells in postnatal mice. While the prevalence of GFP(+) cells in testis rapidly declined with age, the skin-resident GFP(+) population expanded in a cyclical fashion. These cells were identified as epidermal stem cells dwelling in the stem cell niche of the hair follicle, which endogenously expressed all principle reprogramming factors at low levels. Interestingly, skin wounding or non-traumatic hair removal robustly expanded the GFP(+) epidermal cell pool not only locally, but also in uninjured skin areas, demonstrating the existence of a systemic response. Thus, the epithelial stem cell niche of the hair follicle harbors an expandable pool of Oct4+ stem cells, which might be useful for therapeutic cell transfer or facilitated reprogramming.

No MeSH data available.


Related in: MedlinePlus