Hash4, a novel human achaete-scute homologue found in fetal skin

Jönsson, Mikael; Mark, Elisabeth Björntorp; Brantsing, Camilla; Brandner, Johanna M.; Lindahl, Anders; Asp, Julia

doi:10.1016/j.ygeno.2004.07.004

Cited by 21 publications

(17 citation statements)

References 36 publications

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“…Ascl4 is a bHLH transcription factor, and although not well studied, has been implicated in skin development because of its restricted, high expression in fetal skin (Jonsson et al, 2004). Another uniquely expressed transcription factor was Sox21 , previously characterized in cells of the growing hair cuticle (Kiso et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin

et al. 2015

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SUMMARY Defining the unique molecular features of progenitors and their niche requires a genome-wide, whole-tissue approach with cellular resolution. Here we co-isolate embryonic hair follicle (HF) placode and dermal condensate cells, precursors of adult HF stem cells and the dermal papilla/sheath niche, along with lineage-related keratinocytes and fibroblasts, Schwann cells, melanocytes, and a population inclusive of all remaining skin cells. With next-generation RNA-sequencing we define gene expression patterns in the context of the entire embryonic skin, and through transcriptome cross-comparisons we uncover hundreds of enriched genes in cell type-specific signatures. Axon guidance signaling and many other pathway genes are enriched in multiple signatures, implicating these factors in driving the large-scale cellular rearrangements necessary for HF formation. Finally, we share all data in an interactive, searchable companion website. Our study provides an overarching view of signaling within the entire embryonic skin and captures a molecular snapshot of HF progenitors and their niche.

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Section: Resultsmentioning

confidence: 99%

An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin

et al. 2015

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“…ASCL3 encodes a transcription factor highly involved in determination of cell fate and the development and differentiation of numerous tissues (Yoshida et al, 2001; Jonsson et al, 2004). …”

Section: Discussionmentioning

confidence: 99%

Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

et al. 2016

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Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

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“…To search for new bHLH genes, the bioinformatics tools provided by the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov) were used as previously described (Jonsson et al 2004). Briefly, protein sequences of Scleraxis (accession no.…”

Section: Database Searchmentioning

confidence: 99%

“…Northern blot analysis was performed as described previously (Jonsson et al 2004) with some minor modifications; 2.8 μg mRNA was loaded onto the gel containing 0.66 M formaldehyde, and Rapid-hyb buffer was used for probe hybridization (Amersham Biosciences, Buckinghamshire, England). An MTN blot containing four human fetal tissues (liver, brain, lung, and kidney) was also hybridized according to the manufacturer's instructions (Clontech).…”

Section: Rt-pcr Protocolmentioning

confidence: 99%

Notch and HES5 are regulated during human cartilage differentiation

et al. 2006

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The molecular mechanisms of cartilage differentiation are poorly understood. In a variety of tissues other than cartilage, members of the basic helix-loop-helix (bHLH) family of transcription factors have been demonstrated to play critical roles in differentiation. We have characterized the human bHLH gene HES5 and investigated its role during chondrogenesis. Blockage of the Notch signaling pathway with a gamma-secretase inhibitor has demonstrated that the human HES5 gene is a downstream marker of Notch signaling in articular chondrocytes. Markers for the Notch signaling pathway significantly decrease during cartilage differentiation in vitro. Cell proliferation assayed by using BrdU has revealed that blockage of Notch signaling is associated with significantly decreased proliferation. Northern blot and reverse transcription/polymerase chain reaction of a panel of various tissues have shown that HES5 is transcribed as a 5.4-kb mRNA that is ubiquitously expressed in diverse fetal and adult tissues. Articular cartilage from HES5(-/-) and wild-type mice has been analyzed by using various histological stains. No differences have been detected between the wild-type and HES5(-/-) mice. Our data thus indicate that the human HES5 gene is coupled to the Notch receptor family, that expression of Notch markers (including HES5) decreases during cartilage differentiation, and that the blockage of Notch signaling is associated with significantly decreased cell proliferation.

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Hash4, a novel human achaete-scute homologue found in fetal skin

Cited by 21 publications

References 36 publications

An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin

An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin

Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

Notch and HES5 are regulated during human cartilage differentiation

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