Gene module reconstruction identifies cellular differentiation processes and the regulatory logic of specialized secretion in zebrafish.

Autor:	Wang Y; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Biozentrum, University of Basel, Basel 4056, Switzerland., Liu J; Biozentrum, University of Basel, Basel 4056, Switzerland; Allen Discovery Center for Cell Lineage Tracing, University of Washington, Seattle, WA 98195, USA., Du LY; Biozentrum, University of Basel, Basel 4056, Switzerland; Allen Discovery Center for Cell Lineage Tracing, University of Washington, Seattle, WA 98195, USA., Wyss JL; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA., Farrell JA; Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Electronic address: jeffrey.farrell@nih.gov., Schier AF; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Biozentrum, University of Basel, Basel 4056, Switzerland; Allen Discovery Center for Cell Lineage Tracing, University of Washington, Seattle, WA 98195, USA. Electronic address: alex.schier@unibas.ch.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Nov 22. Date of Electronic Publication: 2024 Nov 22.
DOI:	10.1016/j.devcel.2024.10.015
Abstrakt:	During differentiation, cells become structurally and functionally specialized, but comprehensive views of the underlying remodeling processes are elusive. Here, we leverage single-cell RNA sequencing (scRNA-seq) developmental trajectories to reconstruct differentiation using two secretory tissues as models-the zebrafish notochord and hatching gland. First, we integrated expression and functional similarities to identify gene modules, revealing dozens of modules representing known and newly associated differentiation processes and their dynamics. Second, we focused on the unfolded protein response (UPR) transducer module to study how general versus cell-type-specific secretory functions are regulated. Profiling loss- and gain-of-function embryos identified that the UPR transcription factors creb3l1, creb3l2, and xbp1 are master regulators of a general secretion program. creb3l1/creb3l2 additionally activate an extracellular matrix secretion program, while xbp1 partners with bhlha15 to activate a gland-like secretion program. Our study presents module identification via multi-source integration for reconstructing differentiation (MIMIR) and illustrates how transcription factors confer general and specialized cellular functions. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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