Blimp1 Defines a Progenitor Population that Governs Cellular Input to the Sebaceous Gland

Abstract

Epidermal lineage commitment occurs when multipotent stem cells are specified to three lineages: the epidermis, the hair follicle, and the sebaceous gland (SG). How and when a lineage becomes specified remains unknown. Here, we report the existence of a population of unipotent progenitor cells that reside in the SG and express the transcriptional repressor Blimp1. Using cell-culture studies and genetic lineage tracing, we demonstrate that Blimp1-expressing cells are upstream from other cells of the SG lineage. Blimp1 appears to govern cellular input into the gland since its loss leads to elevated c-myc expression, augmented cell proliferation, and SG hyperplasia. Finally, BrdU labeling experiments demonstrate that the SG defects associated with loss of Blimp1 lead to enhanced bulge stem cell activity, suggesting that when normal SG homeostasis is perturbed, multipotent stem cells in the bulge can be mobilized to correct this imbalance.

Development and Homeostasis of the Skin Epidermis

“…Lineage tracing using K15CREPR mice showed labeling of rare SG cells (Morris et al 2004), whereas Lgr5 (Jaks et al 2008) and K19CREER failed to label the SG during homeostasis Lapouge et al 2011). In contrast, during pathological conditions that stimulate SG proliferation such as oncogenic Ras expression (Lapouge et al 2011) or Blimp1 deletion (Horsley et al 2006), bulge SCs can contribute to the expansion of SG. Under physiological conditions, the SG contains its own unipotent progenitors that ensure its high cellular turnover.…”

“…2) characterized by the expression of the cell surface markers MTS24, Lrig1, Blimp1, or Lgr6, which are able to differentiate into all epidermal lineages upon transplantation into immunodeficient mice (Horsley et al 2006;Nijhof et al 2006;Jensen et al 2008Jensen et al , 2009Snippert et al 2010). Lgr6 lineage-tracing experiments showed that these cells contribute to SG homeostasis but also mark some cells in the interfollicular epidermis (IFE) (Snippert et al 2010).…”

Identification and expression profiles of prdm1 in medaka Oryzias latipes

“…Except of functions in immune-related cells, Prdm1 plays key roles in the development of a wide variety of tissues in mice [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. In mice, Prdm1 is expressed in endoderm, mesoderm and ectoderm-derived tissues during embryonic development [37].…”

“…In mice, Prdm1 is expressed in endoderm, mesoderm and ectoderm-derived tissues during embryonic development [37]. Prdm1 governs germ cell specification [23][24][25] and regulates development of the sebaceous gland [26], skin epidermis [27], the posterior forelimb, caudal pharyngeal arches, sensory vibrissae, heart [28], photoreceptor [29], and intestine [30,31]. Prdm1 also is a tumor suppressor in blood cells [32][33][34][35] by regulating P53 expression [36].…”

Ephrins Negatively Regulate Cell Proliferation in the Epidermis and Hair Follicle

“…However, there is also evidence for distinct stem cell populations in the sebaceous gland as well as the interfollicular epidermis [10,11]. Unifying these data suggests the existence of distinct stem cell populations, which can, under the appropriate stimuli or injury, contribute to and regenerate several epidermal lineages.…”