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Quaking regulates lineage-specific splicing patterns between early progenitor cells and is required for cardiac cell fate specification

ABSTRACT: Cell type-specific alternative splicing (AS) regulates tissue homeostasis, with several examples of AS promoting stem cell self-renewal or differentiation. However, the lineage-specific patterns of AS required for early progenitor cells of each of the three germ layers and the specific RNA binding proteins (RBPs) essential for early cell fate are unknown. To approach this question, we performed parallel RNA-seq on human embryonic stem cells (hESCs), hESC-derived definitive endoderm (DE), cardiac mesoderm (CM), and ectoderm (ECT) cells. Analysis of AS patterns in these datasets show that, unlike ECT cells, DE and CM cells display distinct and non-overlapping patterns of lineage-specific splicing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162649 | GEO | 2022/04/19

REPOSITORIES: GEO

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Project description:deBack2012 - Lineage Specification in Pancreas Development This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells. This model is described in the article: On the role of lateral stabilization during early patterning in the pancreas de Back W., Zhou JX, Brusch L J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766 Abstract: The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development. This model is hosted on BioModels Database and identified by: MODEL1211010000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Quaking regulates lineage-specific splicing patterns between early progenitor cells and is required for cardiac cell fate specification

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