Bulk RNA-Seq datasets supporting a common precursor expression program leading to brain pericyte differentiation from neural crest and mesoderm

Brain pericytes are critical for regulating endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. How the developmental acquisition of pericytes to naked endothelium is regulated, is largely unknown, but is relevant to disorders where vessels are poorly stabilized. Although pericytes are derived from neural crest and mesoderm, brain pericytes from both origins are currently indistinguishable; the genetic pathways leading to a convergent pericyte phenotype are unknown. We show here that a precursor population expressing the transcription factor nkx3.1 with origins in both NCC and mesoderm, develops into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1, foxf2a, and cxcl12b -expressing pericyte precursor population is present around the cxcr4 expressing basilar artery, and that these cells later spread throughout the brain. Cxcl12b- Cxcr4 signaling is required for pericyte attachment and differentiation but not for later pericyte development. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number. Thus, we have defined an undescribed population of pericyte precursors and identified genes critical for their differentiation. Overall design: 30 hpf nkx3.1ca116 mutant and wild type embryos were collected and RNA prepared using Trizol (ThermoFisher, Waltham MA). Libraries were prepared from total mRNA per sample using the Illumina Ultra II directional RNA library prep (SanDiego, CA), and sequenced via the NovaSeq SP 100 cycle v 1.5 sequencing run with 33 million reads per sample. 4 replicates were sequenced per condition.