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Foxi1 regulates multipotent mucociliary progenitors and ionocyte specification through transcriptional and epigenetic mechanisms

ABSTRACT: Foxi1 regulates multipotent mucociliary progenitors and ionocyte specification through transcriptional and epigenetic mechanisms

PROVIDER: PRJNA1276124 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33962400_1.fastq.gz	Fastqsanger.gz
	SRR33962400_2.fastq.gz	Fastqsanger.gz
	SRR33962401_1.fastq.gz	Fastqsanger.gz
	SRR33962401_2.fastq.gz	Fastqsanger.gz
	SRR33962402_1.fastq.gz	Fastqsanger.gz

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Foxi1 regulates multipotent mucociliary progenitors and ionocyte specification through transcriptional and epigenetic mechanisms

Project description:Foxi1 is a master regulator of ionocytes (ISCs / INCs) across species and organs. Two subtypes of ISCs exist, and both - and -ISCs regulate pH- and ion-homeostasis in epithelia. Gain and loss of FOXI1 function are associated with human diseases, including Pendred syndrome, male infertility, renal acidosis and cancers. Foxi1 was predominantly studied in the context of ISC specification, however, reports indicate additional functions in early and ectodermal development. Here, we re-investigated the functions of Foxi1 in Xenopus laevis embryonic mucociliary epidermis development and found a novel function for Foxi1 in the generation of Notch-ligand expressing mucociliary multipotent progenitors (MPPs). We demonstrate that Foxi1 has multiple concentration-dependent functions: At low levels, Foxi1 maintains ectodermal competence in MPPs through transcriptional and epigenetic mechanisms, while at high levels, Foxi1 induces a multi-step process of ISC specification and differentiation in cooperation with Ubp1 and Dmrt2. We further describe how foxi1 expression is affected through auto- and Notch-regulation, and how this developmental program affects mucociliary patterning. Together, we reveal novel functions for Foxi1 in Xenopus mucociliary epidermis formation, relevant to our understanding of vertebrate development and human disease.

2025-06-17 | GSE299718 | GEO

Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms

Project description:Foxi1 is a master regulator of ionocytes (ISCs) across species and organs. Two subtypes of ISCs exist, and both a- and b-ISCs regulate pH- and ion-homeostasis in epithelia. Gain and loss of Foxi1 function are associated with human diseases, including Pendred syndrome, male infertility, kidney malfunction and cancers. Foxi1 functions were predominantly studied in the context of ISC specification, however, reports indicate additional functions in early and ectodermal development. Here, we re-investigated the functions of Foxi1 to Xenopus laevis embryonic mucociliary epidermis development and found a novel function for Foxi1 in the generation of Notch-ligand expressing mucociliary multipotent progenitors (MPPs). We demonstrate that Foxi1 has multiple concentration-dependent functions: At low levels, Foxi1 confers ectodermal competence through transcriptional and epigenetic mechanisms, while at high levels, Foxi1 induces a multi-step process of ISC specification and differentiation. We further describe how foxi1 expression is affected through auto- and Notch-regulation, how Ubp1 and Dmrt2 regulate ISC subtype differentiation, and how this developmental program affects Notch signaling as well as mucociliary patterning. Together, we reveal novel functions for Foxi1 in Xenopus mucociliary epidermis formation, relevant to our understanding of vertebrate development and human disease.

2024-11-03 | GSE280790 | GEO

Extensive epigenetic priming in multipotent progenitors precedes lineage specification in B-lymphocyte development.

Project description:Extensive epigenetic priming in multipotent progenitors precedes lineage specification in B-lymphocyte development.

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Extensive epigenetic priming in multipotent progenitors precedes lineage specification in B-lymphocyte development.

Project description:B-lymphocyte development is dependent on the interplay between the chromatin landscape and lineage specific transcription factors. It has been suggested that B-lineage commitment is associated with major changes in the nuclear chromatin environment proposing a critical role for lineage specific transcription factors in the formation of the epigenetic landscape. In this report we have used chromosome conformation capture in combination with ATAC-seq analysis to enable highly efficient annotation of both proximal and distal transcriptional control elements to genes activated in B-lineage specification. A large majority of these genes were annotated to at least one regulatory element with an accessible chromatin configuration in multipotent progenitors. Furthermore, the majority of binding sites for the key regulators of B-lineage specification, EBF1 and PAX5, occurred in already accessible regions. EBF1 did, however, cause a dynamic change in ATAC-accessibility and was critical for an increase in distal promoter-enhancer interactions as well as high deposition of chromatin modulating co-factors associated with the establishment of the B-lineage program. Our data unravel an unappreciated level of epigenetic priming at regulatory elements annotated to lineage restricted genes and provide insight into the mechanisms by which lineage specific transcription factors act via already accessible elements in lineage specification.

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Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms

Project description:Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms

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Apical progenitors remain multipotent throughout cortical neurogenesis

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Early lineage segregation of multipotent embryonic mammary gland progenitors [RNA-seq I]

Project description:The mammary gland (MG) is composed of basal cells (BCs) and luminal cells (LCs). While it is generally believed that MG arises from embryonic multipotent progenitors (EMPs), it remains unclear when lineage restriction occurs and what are the mechanisms responsible for the switch from multipotency to unipotency during MG morphogenesis. Here, we performed multicolor lineage tracing and assessed the fate of single progenitors and demonstrated the existence of a developmental switch from multipotency to unipotency during embryonic MG development. Molecular profiling and single cell RNA-seq revealed that EMPs express a unique hybrid basal and luminal signature and the factors associated with the different lineages. Sustained p63 expression in EMPs promotes unipotent BC fate and was sufficient to reprogram adult LCs into BCs by promoting an intermediate hybrid multipotent like state. Altogether, this study identifies the timing and the mechanisms mediating the early lineage segregation of multipotent progenitors during MG development.

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