NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices

Adam, René; Yang, Hanseul; Ge, Yejing; Infarinato, Nicole R.; Gur-Cohen, Shiri; Miao, Yanying; Wang, Ping; Zhao, Yilin; Lu, Catherine P.; Kim, Jeong Eun; Ko, Joo Yeon; Paik, Seung Sam; Gronostajski, Richard M.; Kim, Jaehwan; Krueger, James G.; Zheng, Deyou; Fuchs, Elaine

doi:10.1038/s41556-020-0513-0

Cited by 61 publications

(55 citation statements)

References 71 publications

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“…This allowed increased accessibility to binding motifs of wound‐induced TFs such as AP1 and Foxo1, previously discovered by the group to promote HF‐to‐epidermis lineage infidelity 80 . Subsequent scRNA‐seq analysis also confirmed highly reduced bulge HFSC signature gene expression in purified NFI dKO HFSCs as well 79 . Their findings specify NFI TFs as a previously unknown mechanism that HFSCs employ against epidermal fate conversion during homeostasis.…”

Section: Transcription Factors and Signalling Pathways Acting In Quiementioning

confidence: 69%

“…80 Subsequent scRNA-seq analysis also confirmed highly reduced bulge HFSC signature gene expression in purified NFI dKO HFSCs as well. 79 Their findings specify NFI TFs as a previously unknown mechanism that HFSCs employ against epidermal fate conversion during homeostasis. Another intriguing role NFIB seems to play is regulating melanocyte SCs located adjacent to HFSCs through Edn2/EdnrB signalling, 81 which we will discuss in more depth else-…”

Section: Ta B L E 1 (Continued)mentioning

confidence: 95%

“…human scarring alopecia-like phenotypes in Nfib and Nfix double knockout (NFI dKO) mice. 79 Further analysis using ATAC-seq and ChIP-seq indicated NFI dKO HFSCs had altered chromatin structure. This allowed increased accessibility to binding motifs of wound-induced TFs such as AP1 and Foxo1, previously discovered by the group to promote HF-to-epidermis lineage infidelity.…”

Section: Ta B L E 1 (Continued)mentioning

confidence: 99%

“…Nuclear Factor I (NFI) transcription factors NFIB and NFIX are known for their roles regulating progenitor differentiations during embryonic nervous system development 77,78 . Recent findings from the Fuchs laboratory revealed that NFI TFs also play vital roles in preserving the HFSC identity, the loss of which leads to human scarring alopecia‐like phenotypes in Nfib and Nfix double knockout (NFI dKO) mice 79 . Further analysis using ATAC‐seq and ChIP‐seq indicated NFI dKO HFSCs had altered chromatin structure.…”

Section: Transcription Factors and Signalling Pathways Acting In Quiementioning

confidence: 99%

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Stem cell‐intrinsic mechanisms regulating adult hair follicle homeostasis

Lee

Tumbar

2020

Experimental Dermatology

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Adult stem cell (SC) identity and potential to regenerate tissues are defined by specific combinations of cell-intrinsic molecular mechanisms that control gene expression, in particular transcription. 1,2 These mechanisms include chromatin structure, transcription factors, DNA regulatory elements such as enhancers and non-coding RNAs. Cell metabolism is another emergent cell-intrinsic mechanism of SC regulation. 3,4 Furthermore, SCs respond to microenvironmental (or niche) signals as well as signal themselves to the surrounding microenvironment for reciprocal control of cell behaviour and tissue homeostasis. 1,5 All these mechanisms collectively govern cell growth and proliferation, cell adhesion, migration, and differentiation, and maintain SC regenerative potential throughout life.

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Section: Transcription Factors and Signalling Pathways Acting In Quiementioning

confidence: 69%

Section: Ta B L E 1 (Continued)mentioning

confidence: 95%

Section: Ta B L E 1 (Continued)mentioning

confidence: 99%

Section: Transcription Factors and Signalling Pathways Acting In Quiementioning

confidence: 99%

See 2 more Smart Citations

Stem cell‐intrinsic mechanisms regulating adult hair follicle homeostasis

Lee

Tumbar

2020

Experimental Dermatology

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“…In another recent study, the loss of nuclear factor IB (Nfib) and IX (Nfix) revealed the abolition of the epigenetic landscape of super-enhancers with the inability to maintain hfSCs stemness ( Adam et al, 2020 ). In addition, expression of NFATc1 is directly controlled by canonical BMP/Smad1/5/8 signaling in the hfSCs quiescence, since the NFATc1 promoter possesses Smad’s binding sites ( Horsley et al, 2008 ; Kandyba et al, 2013 ; Genander et al, 2014 ).…”

Section: Stemness Of Hair Follicle Stem Cells and Regenerative Potentmentioning

confidence: 99%

An Intrinsic Oscillation of Gene Networks Inside Hair Follicle Stem Cells: An Additional Layer That Can Modulate Hair Stem Cell Activities

Daszczuk

Mazurek

Pieczonka

et al. 2020

Front. Cell Dev. Biol.

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This article explores and summarizes recent progress in and the characterization of main players in the regulation and cyclic regeneration of hair follicles. The review discusses current views and discoveries on the molecular mechanisms that allow hair follicle stem cells (hfSCs) to synergistically integrate homeostasis during quiescence and activation. Discussion elaborates on a model that shows how different populations of skin stem cells coalesce intrinsic and extrinsic mechanisms, resulting in the maintenance of stemness and hair regenerative potential during an organism’s lifespan. Primarily, we focus on the question of how the intrinsic oscillation of gene networks in hfSCs sense and respond to the surrounding niche environment. The review also investigates the existence of a cell-autonomous mechanism and the reciprocal interactions between molecular signaling axes in hfSCs and niche components, which demonstrates its critical driving force in either the activation of whole mini-organ regeneration or quiescent homeostasis maintenance. These exciting novel discoveries in skin stem cells and the surrounding niche components propose a model of the intrinsic stem cell oscillator which is potentially instructive for translational regenerative medicine. Further studies, deciphering of the distribution of molecular signals coupled with the nature of their oscillation within the stem cells and niche environments, may impact the speed and efficiency of various approaches that could stimulate the development of self-renewal and cell-based therapies for hair follicle stem cell regeneration.

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Methods to Identify Immune Cells in Tissues With a Focus on Skin as a Model

2022

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The skin protects our body from external challenges, insults, and pathogens and consists of two layers, epidermis and dermis. The immune cells of the skin are an integral part of protecting the body and essential for mediating skin immune homeostasis. They are distributed in the epidermal and dermal layers of the skin. Under homeostatic conditions, the mouse and human skin epidermis harbors immune cells such as Langerhans cells and CD8 + T cells, whereas the dermis contains dendritic cells (DCs), mast cells, macrophages, T cells, and neutrophils. Skin immune homeostasis is maintained through communication between epidermal and dermal cells and soluble factors. This communication is important for proper recruitment of immune cells in the skin to mount immune responses during infection/injury or in response to external/internal insults that alter the local cellular milieu. Imbalance in this crosstalk that occurs in association with inflammatory skin disorders such as psoriasis and atopic dermatitis can lead to alterations in the number and type of immune cells contributing to pathological manifestation in these disorders. Profiling changes in the immune cell type, localization, and number can provide important information about disease mechanisms and help design interventional therapeutic strategies. Toward this end, skin cells can be detected and characterized using basic techniques like immunofluorescence, immunohistochemistry, and flow cytometry, and recently developed methods of multiplexing. This article provides an overview on the basic techniques that are widely accessible to researchers to characterize immune cells of the skin.

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NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices

Cited by 61 publications

References 71 publications

Stem cell‐intrinsic mechanisms regulating adult hair follicle homeostasis

Stem cell‐intrinsic mechanisms regulating adult hair follicle homeostasis

An Intrinsic Oscillation of Gene Networks Inside Hair Follicle Stem Cells: An Additional Layer That Can Modulate Hair Stem Cell Activities

Methods to Identify Immune Cells in Tissues With a Focus on Skin as a Model

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