CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development.
Edroaldo Lummertz da RochaCaroline KubaczkaWade W SugdenMohamad Ali NajiaRan JingArianna MarkelZachary C LeBlancRafael Dos Santos PeixotoMarcelo FalchettiJames J CollinsTrista E NorthGeorge Q DaleyPublished in: Nature cell biology (2022)
Intercellular communication orchestrates a multitude of physiologic and pathologic conditions. Algorithms to infer cell-cell communication and predict downstream signalling and regulatory networks are needed to illuminate mechanisms of stem cell differentiation and tissue development. Here, to fill this gap, we developed and applied CellComm to investigate how the aorta-gonad-mesonephros microenvironment dictates haematopoietic stem and progenitor cell emergence. We identified key microenvironmental signals and transcriptional networks that regulate haematopoietic development, including Stat3, Nr0b2, Ybx1 and App, and confirmed their roles using zebrafish, mouse and human models. Notably, CellComm revealed extensive crosstalk among signalling pathways and convergence on common transcriptional regulators, indicating a resilient developmental programme that ensures dynamic adaptation to changes in the embryonic environment. Our work provides an algorithm and data resource for the scientific community.
Keyphrases
- single cell
- transcription factor
- machine learning
- endothelial cells
- gene expression
- cell therapy
- healthcare
- deep learning
- stem cells
- mental health
- randomized controlled trial
- neoadjuvant chemotherapy
- cell proliferation
- squamous cell carcinoma
- pulmonary artery
- study protocol
- radiation therapy
- clinical trial
- big data
- coronary artery
- oxidative stress
- induced pluripotent stem cells
- artificial intelligence
- double blind