Krzysztof Kobielak

University of Southern California | USC · Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC

Mice hair follicles (HFs) are a valuable model for studying various aspects of hair biology, including morphogenesis, development, and regeneration due to their easily observable phenotype and genetic manipulability. The initiation and progression of hair follicle morphogenesis, as well as the hair follicle cycle, are regulated by various signaling...

Hair follicle is a dynamic mini-organ undergoing cyclic phases of growth, degradation and quiescence. Our previous findings, revealed that this process is dependent on competitive balance between two well-known molecular pathways, wingless/integrated pathway (WNT) and bone morphogenetic protein pathway (BMP) in hair follicle stem cells (hfSCs). In...

AIMS Our hypothesis is that NPFSCs are a crucial source of cells during nail homeostasis and are necessary to respond after the injury to regenerate not only the nail but also digit in mammals. Moreover, we want to prove, that the BMP pathway is critical and upstream of Wnt activation in a distal matrix and digit regeneration, however, the correlat...

Hair follicles (HFs) are an excellent model for studying the underlying mechanisms that regulate hair follicle stem cells (hfSCs) homeostasis. The behavior of hfSCs is tightly governed by an intricate balance of two known signaling pathways: BMP and WNT that interplay to induce bouts of hfSCs quiescence and activation. We have previously shown that...

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the na...

The hair follicle in the sense of a mini-organ is an excellent model for studying molecular mechanisms that governance the transition between quiescence and cyclic activation of the hair follicle stem cells (hfSCs) during the hair growth. Our previous finding, revealed that competitive balance between two well known molecular pathways, wingless/int...

Differential gene expression orchestrates stem cells homeostasis and is controlled by genomic cis-regulatory elements (CRE) regulated by distinct signaling pathways e.g. BMP (Bone Morphogenetic Protein) or WNT (wingless/integrated). CREs serve as platforms for binding of transcription factors (TFs) and transcriptional regulators (TRs), facilitating...

Hair follicle (HF) is a dynamic miniorgan which undergoes cyclic phases of growth, degradation and quiescence. Recently, we discovered molecular mechanism of Bone Morphogenetic Protein (BMP) signaling governs the homeostasis of hair follicle Stem Cells (hfSCs). Smad1, 5 and 8/9 are signal transducers and transcriptional modulators activated by phos...

The cutaneous wound-healing program is a product of a complex interplay among diverse cell types within the skin. One fundamental process that is mediated by these reciprocal interactions is the mobilization of local stem cell pools to promote tissue regeneration and repair. Using the ablation of epidermal caspase-8 as a model of wound healing in M...

ELife digest Skin includes hundreds of thousands of hair follicles that cycle through different stages of activity. Each follicle grows hair, sometimes (in the case of long hairs like human head hair and horse tail hairs) for several years, before losing it. The follicle then goes through a resting stage before starting to grow another hair. To ach...

Dataset 1: Putative activator genes (tabs #1, #2) and putative inhibitor genes (tabs #3, #4) available from a whole skin microarray dataset. DOI: http://dx.doi.org/10.7554/eLife.22772.010

Dataset 2: Putative activator and inhibitor genes displaying domain-specific expression patterns at all hair cycle time points on whole skin RNA-seq profiling. Genes are grouped into individual tabs based on (i) their activator or inhibitor expression profile and (ii) their specificity to one or several skin domains. DOI: http://dx.doi.org/10.7554/...

Dataset 3: Differentially expressed genes specific to refractory telogen dorsal skin, telogen ear skin and cartilage/muscle complex. DOI: http://dx.doi.org/10.7554/eLife.22772.012

Abstract In this chapter we summarize recent progress in the characterization of different skin stem cell populations and their roles in epidermis, hair follicle, and sweat gland regeneration during homeostasis and injury. We discuss new discoveries in the differentiation capabilities of both embryonic stem cells and induced pluripotent stem cells...

How tissue patterns form in development and regeneration is a fundamental issue remaining to be fully understood. The integument often forms repetitive units in space (periodic patterning) and time (cyclic renewal), such as feathers and hairs. Integument patterns are visible and experimentally manipulatable, helping us reveal pattern formative proc...

Significance Skin appendages including hair follicles, sweat glands, and nails offer a source of regenerative support following injury. Here, we focus on the regenerative potential of the peri-nail region and reveal a population of K15-positive, label retaining cells (LRCs) within the nail proximal fold with self-renewal capabilities. Physiological...

Adult stem cells (SCs) are important to maintain homeostasis of tissues including several mini-organs like hair follicles and sweat glands. However, the existence of stem cells in minor salivary glands (SGs) is largely unexplored. In vivo histone2B GFP (H2BGFP) pulse chase strategy has allowed us to identify slow cycling, label retaining cells (LRC...

The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis and progeny differentiation. During morphogenesis, Wnt signaling is well characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required...

Hair follicles (HFs) are regenerative mini-organs that offer a highly informative model system to study the regulatory mechanisms of hair follicle stem cells (hfSCs) homeostasis and differentiation. Bone Morphogenetic Protein (BMP) signaling is key in both of these processes, governing hfSCs quiescence in the bulge and differentiation of matrix pro...

Slow cycling is a common feature shared among several stem cells (SCs) identified in adult tissues including hair follicle and cornea. Recently, existence of unipotent SCs in basal and lumenal layers of sweat gland (SG) has been described and label retaining cells (LRCs) have also been localized in SGs; however, whether these LRCs possess SCs chara...

Histone deacetylases (HDAC) are present in the epidermal layer of the skin, outer root sheath and hair matrix. To investigate how histone acetylation affects skin morphogenesis and homeostasis, mice were generated with a K14 promoter-mediated reduction of Hdac1 or Hdac2. The skin of HDAC1 null (K14-Cre Hdac1cKO/cKO) mice exhibited a spectrum of les...

Hair follicles facilitate the study of stem cell behavior because stem cells in progressive activation stages, ordered within the follicle architecture, are capable of cyclic regeneration. To study the gene network governing the homeostasis of hair bulge stem cells, we developed a Keratin 15-driven genetic model to directly perturb molecular signal...

We have investigated the structure of the EDA gene in a patient with the clinical symptoms of anhidrotic ectodermal dysplasia (EDA). Electrophoretic analysis of the amplified fragment of exon 5 of the EDA gene in the affected boy revealed a PCR product that was shorter by 20 bp than the same fragment obtained from a healthy individual. A similar sh...

During the hair cycle, follicle stem cells (SCs) residing in a specialized niche called the “bulge” undergo bouts of quiescence and activation to cyclically regenerate new hairs. Developmental studies have long implicated the canonical bone morphogenetic protein (BMP) pathway in hair follicle (HF) determination and differentiation, but how BMP sign...

Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of...

The structure of the EDA1 gene was investigated in a patient with anhidrotic ectodermal dysplasia. Sequence analysis revealed a novel A1270G transition in exon 9 of the EDA1 gene in the patient and his uncle, whereas the patient's mother and grandmother were heterozygotes. This mutation resulted in Tyr343Cys substitution in the extracellular domain...

Recent developments of the investigations on the molecular basis of anhidrotic ectodermal dysplasia are reviewed. Identification of the major product of the EDA gene (ectodysplasin A), a protein belonging to a group of TNF ligands, and molecular cloning of the cDNA, encoding its receptor (EDAR), a member of the TNF receptor family, are presented. T...

Anhidrotic ectodermal dysplasia (EDA) is caused by mutations in the EDA gene encoding ectodysplasin A, a member of the TNF ligand superfamily involved in the communication between the cells. The structure of the EDA gene was investigated in three patients exhibiting clinical symptoms of EDA in an attempt to correlate the molecular findings with the...

Anhidrotic ectodermal dysplasia (EDA) is caused by mutations in the EDA gene encoding ectodysplasin A, a member of the TNF ligand superfamily involved in the communication between the cells. The structure of the EDA gene was investigated in three patients exhibiting clinical symptoms of EDA in an attempt to correlate the molecular findings with the...

Lymphoid enhancer-binding factor-1 (LEF-1), a member of the high mobility group (HMG) family of proteins, regulates expression of T-cell receptor-alpha gene and is one of the key regulatory molecules in the epithelial-mesenchymal interactions during embryonic development. Among others, LEF-1 regulates expression of cytokeratin genes involved in for...

Oligodontia, sparse hair and deficiency of eccrine sweat glands are the features characteristic for the phenotype of the patients with anhidrotic ectodermal dysplasia (EDA). This syndrome is caused by mutations in the EDA or DL (downless) genes, encoding members of the TNF ligand and TNF receptor families, involved in the communication between the...

It has been reported that two genes MSX1 and PAX9, which encode transcription factors, are associated with selective tooth agenesis. Expression of these genes specifically marks the regions of the mesenchyme where the tooth buds are formed. A mutation in the MSX1 gene, detected in a single family, resulting in an Arg-->Pro substitution in the homeo...

We have cloned and sequenced rat cDNA that encodes the Lef-1 protein. The cDNA, containing 1194 nt exhibits 94% similarity to the mouse Lef-1 cDNA. The deduced amino-acids sequence of rat Lef-1 protein, consisting of 397 amino acids, exhibited 98% homology with the known sequence of mouse Lef-1 protein.

This review is focused on recent developments of the genetic studies on anhidrotic ectodermal dysplasia (EDA) reported since the publication of our previous review in 1997. In addition to cloning of the mouse homologue of the EDA gene, the Tabby gene, recent discoveries of the novel transcript isoforms by several research groups as well as by our g...

We have investigated a fragment of the regulatory region of the EDA gene in a patient with clinical symptoms of anhidrotic ectodermal dysplasia (EDA), whose DNA sequence of exon 1 was normal. The single-strand conformation polymorphism (SSCP) analysis of PCR-amplified fragments of the regulatory region of the EDA gene suggested a mutation localized...

The evidence from literature strongly suggests that Christ-Siemens-Touraine (CST) syndrome is associated with mutations of the newly discovered EDA gene. The gene is situated on the long arm of the X chromosome (Xq12.2-q13.1) and contains two exons separated by a 200 kbp intron. The 5′-untranslated region and most of the coding sequence are localiz...