Dataset Information

Dynamic regulation of chromatin accessibility during melanocyte stem cell activation

ABSTRACT: Dynamic regulation of chromatin accessibility during melanocyte stem cell activation

PROVIDER: PRJNA974408 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR24918261.fastq.gz	Fastqsanger.gz
	SRR24918262.fastq.gz	Fastqsanger.gz
	SRR24918263.fastq.gz	Fastqsanger.gz

Items per page:

1 - 3 of 3

Similar Datasets

Project description:Dysfunctions in melanocytes can lead to pigmentation disorders, such as albinism, or contribute to the development of melanoma, the most aggressive form of skin cancer. Epidermal melanocytes typically interact with the collagen IV-rich basement membrane, but upon injury or in pathological conditions, they can encounter environments rich in collagen I or fibronectin. While alterations in ECM composition and stiffness are known to impact cell behavior, the specific roles of each of these cues for melanocyte functions remain unclear. To explore the impact of these extrinsic cues, we here exposed murine melanocytes to different ECM proteins as well as varying substrate stiffnesses. This study identified MITF, a key regulator of melanocyte differentiation and function, as an ECM- and mechanosensitive transcription factor. We further revealed that distinct ECM proteins and substrate stiffness engage a FAK/MEK/ERK/MITF signaling axis to control melanocyte functions. Exposure of melanocytes to collagen I restricted FAK and ERK activation, promoting high nuclear MITF levels associated with melanocyte proliferation and differentiation. Conversely, fibronectin elicited elevated FAK and ERK activation, leading to low nuclear MITF, correlating with a dedifferentiated and motile phenotype. Consistent with these observations, RNA sequencing revealed that COL I supports a differentiated gene expression program, whereas FN induces a neural crest-like and dedifferentiated transcriptomic signature. Importantly, inhibiting MEK or ERK activity in melanocytes cultured on fibronectin led to increased MITF nuclear localization, and enhanced melanogenesis. Additionally, we uncovered that melanocyte mechanoresponses differ depending on the specific ECM environment. Together, these findings reveal a synergistic effect of extrinsic cues on melanocyte function, with a context-dependent MITF regulation downstream of ERK, offering new perspectives for our understanding of melanocyte-related pathologies.

Dataset Information

Dynamic regulation of chromatin accessibility during melanocyte stem cell activation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets