PMID- 33934382 OWN - NLM STAT- MEDLINE VI - 40 IP - 10 TI - Employing core regulatory circuits to define cell identity. PG - e106785 CI - © 2021 The Authors. Published under the terms of the CC BY 4.0 license. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Embo J JT - The EMBO journal JID - 8208664 IS - 1460-2075 (Electronic) LID - 10.15252/embj.2020106785 [doi] FAU - Almeida, Nathalia AU - Almeida N AUID- ORCID: 0000-0003-3145-186X AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Chung, Matthew W H AU - Chung MWH AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Drudi, Elena M AU - Drudi EM AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Engquist, Elise N AU - Engquist EN AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Hamrud, Eva AU - Hamrud E AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Isaacson, Abigail AU - Isaacson A AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Tsang, Victoria S K AU - Tsang VSK AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Watt, Fiona M AU - Watt FM AUID- ORCID: 0000-0001-9151-5154 AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. FAU - Spagnoli, Francesca M AU - Spagnoli FM AUID- ORCID: 0000-0001-7094-8188 AD - Centre for Stem Cells and Regenerative Medicine, Guy's Hospital, King's College London, London, UK. IS - 0261-4189 (Linking) RN - 0 (Transcription Factors) SB - IM MH - Humans MH - Regenerative Medicine/*methods MH - Transcription Factors/genetics/metabolism OTO - NOTNLM OT - GRN OT - cell identity OT - core regulatory circuit OT - regenerative medicine OT - transcription factor PMC - PMC8126924 DCOM- 20211112 LR - 20240216 DP - 20210517 DEP - 20210502 AB - The interplay between extrinsic signaling and downstream gene networks controls the establishment of cell identity during development and its maintenance in adult life. Advances in next-generation sequencing and single-cell technologies have revealed additional layers of complexity in cell identity. Here, we review our current understanding of transcription factor (TF) networks as key determinants of cell identity. We discuss the concept of the core regulatory circuit as a set of TFs and interacting factors that together define the gene expression profile of the cell. We propose the core regulatory circuit as a comprehensive conceptual framework for defining cellular identity and discuss its connections to cell function in different contexts.