A Spatiotemporal Cell Atlas of Cardiopulmonary Progenitor Cell Allocation During Development

Abstract

The heart and lung co-orchestrate their development during organogenesis. The mesoderm surrounding both the developing heart and anterior foregut endoderm provides instructive cues guiding cardiopulmonary development. Additionally, it serves as a source of cardiopulmonary progenitor cells (CPPs) expressing Wnt2that give rise to both cardiac and lung mesodermal cell lineages. Despite its critical importance to both heart and lung development, mechanisms guiding CPP specification are unclear. To address this, we lineage traced Wnt2+ CPPs at E8.5 and performed single cell RNA sequencing (scRNA-seq) on collected progeny across the developmental lifespan. Using computational analyses, we created a CPP-derived cell atlas that revealed a previously underappreciated spectrum of CPP-derived cell lineages, including all lung mesodermal lineages, ventricular cardiomyocytes (CMs), and epicardial and pericardial cells. Integrating spatial mapping with computational cell trajectory analysis and transcriptional profiling, we have provided a potential molecular and cellular roadmap for cardiopulmonary development.

Note:

Funding Information: This work was supported through the Parker B. Francis Foundation (D.B.F.), Burroughs Wellcome Foundation Career Award for Medical Scientists (R.J.), and grants from the National Institutes of Health: K08 HL140129 and R56 HL167939 (D.B.F.), R35 HL166663 (R.J.), and R00 HL141684 (J.A.Z.).

Conflict of Interests: All authors declare no competing interests.

Keywords: Cardiopulmonary development, Cell fate, transcription factors