Integrative and perturbation based analysis of the transcriptional dynamics of TGF β/BMP system components in transition from embryonic stem cells to neural progenitors

Schematic illustration of a systems level approach to dissect the transcriptional and intra ‐dependent network of the TGFβ/BMP signaling pathway in embryonic stem cells that gradually differentiate to neural progenitors. AbstractCooperative actions of extrinsic signals and cell ‐intrinsic transcription factors alter gene regulatory networks enabling cells to respond appropriately to environmental cues. Signaling by Transforming Growth Factor type β (TGFβ) family ligands (eg, Bone Morphogenetic Proteins [BMPs] and Activins/Nodal) exerts cell‐type specific and context‐ dependent transcriptional changes, thereby steering cellular transitions throughout embryogenesis. Little is known about coordinated regulation and transcriptional interplay of the TGFβ system. To understand intra‐family transcriptional regulation as part of this system's actions during developme nt, we selected 95 of its components and investigated their mRNA‐expression dynamics, gene‐gene interactions and single‐cell expression heterogeneity in mouse embryonic stem cells (mESCs) transiting to neural progenitors. Interrogation at 24 hour intervals identified 4 types of temporal gene transcription profile that capture all stages,that is, pluripotency, epiblast formation and neural commitment. Then, between each stage we performed esiRNA ‐based perturbation of each individual component and documented the effect on steady‐state mRNA levels of the remaining 94 components. This exposed an in...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research