The ENCODE mouse postnatal developmental time course identifies regulatory programs of cell types and cell states

Area of Science:

• Genomics and Developmental Biology
• Single-cell analysis of gene regulation

Background:

• Postnatal genomic regulation is crucial for tissue maturation but remains under-explored compared to adult or prenatal stages.
• Existing genomic resources often focus on adult tissues or prenatal development, leaving a gap in postnatal understanding.

Purpose of the Study:

• To create the first comprehensive single-nucleus resource of postnatal regulatory events in diverse mouse tissues.
• To identify and characterize cell types, subtypes, and cell states during postnatal development.
• To uncover regulatory programs driving cell differentiation and specialization across multiple tissues.

Main Methods:

• Generated a single-nucleus resource spanning seven postnatal time points and five core mouse tissues.
• Identified 30 cell types (69 subtypes/states) using single-nucleus RNA sequencing.
• Employed Latent Dirichlet Allocation with a curated gene vocabulary to identify regulatory 'topics' linked to cell states.

Main Results:

• Characterized 69 cell types and states, including novel sex-specific adrenal gland populations and early neurogenesis.
• Identified recurrent and cell-type-specific regulatory topics enriched in transcription factors, microRNA host genes, and chromatin regulators.
• Discovered dynamic and sex-specific regulatory elements and transcription factor motifs using chromatin accessibility data.

Conclusions:

• This study provides a foundational resource for postnatal gene regulation in mice, mirroring human development.
• Identified conserved and tissue-specific regulatory programs governing postnatal development and cell specialization.
• Highlights the importance of regulatory factors in driving dynamic transcriptional changes during postnatal maturation.