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A study was conducted to analyze the role of FOXF1 in human lung and intrinsic pulmonary vascular development by describing inactivating mutations in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Findings reveal that patients with deletions harboring FOXF1 genes have not only ACD/MPV but also distinct malformations.

In mammals, multi-tissue regeneration is largely restricted to the distal portion of the digit tip and involves the formation of a blastema, a transient, proliferating cell mass that reforms the diverse tissues of the digit. Historically little was known about the mammalian blastema but with recent advances in single cell transcriptomic approaches and genetic lineage tracing, a more precise understanding of this critical structure has begun to emerge. In this review we summarise the cellular mechanisms underlying adult mammalian digit tip regeneration. We posit that understanding how some mammals naturally regenerate complex tissues will lead to strategies for enhancing regenerative abilities in humans. [ABSTRACT FROM AUTHOR]

Here, we ask why the nail base is essential for mammalian digit tip regeneration, focusing on the inductive nail mesenchyme. We identify a transcriptional signature for these cells that includes Lmx1b and show that the Lmx1b -expressing nail mesenchyme is essential for blastema formation. We use a combination of Lmx1bCreERT2 -based lineage-tracing and single-cell transcriptional analyses to show that the nail mesenchyme contributes cells for two pro-regenerative mechanisms. One group of cells maintains their identity and regenerates the new nail mesenchyme. A second group contributes specifically to the dorsal blastema, loses their nail mesenchyme phenotype, acquires a blastema transcriptional state that is highly similar to blastema cells of other origins, and ultimately contributes to regeneration of the dorsal but not ventral dermis and bone. Thus, the regenerative necessity for an intact nail base is explained, at least in part, by a requirement for the inductive nail mesenchyme. [Display omitted] • Lmx1b+ nail mesenchymal cells possess a unique transcriptional signature • Nail mesenchyme is essential for blastema formation during digit tip regeneration • Nail mesenchymal cells regenerate the new nail mesenchyme • Nail mesenchymal cells contribute to new dorsal dermis and bone via a blastema intermediate Mahmud et al. combine lineage tracing, single-cell transcriptomics, and cell ablations to identify the Lmx1b+ nail mesenchymal cell population that is essential for murine digit tip regeneration. They show that, post amputation, the nail mesenchyme regenerates itself and contributes to the dorsal dermis and bone. [ABSTRACT FROM AUTHOR]

Here, we investigate the origin and nature of blastema cells that regenerate the adult murine digit tip. We show that Pdgfra -expressing mesenchymal cells in uninjured digits establish the regenerative blastema and are essential for regeneration. Single-cell profiling shows that the mesenchymal blastema cells are distinct from both uninjured digit and embryonic limb or digit Pdgfra -positive cells. This unique blastema state is environmentally determined; dermal fibroblasts transplanted into the regenerative, but not non-regenerative, digit express blastema-state genes and contribute to bone regeneration. Moreover, lineage tracing with single-cell profiling indicates that endogenous osteoblasts or osteocytes acquire a blastema mesenchymal transcriptional state and contribute to both dermis and bone regeneration. Thus, mammalian digit tip regeneration occurs via a distinct adult mechanism where the regenerative environment promotes acquisition of a blastema state that enables cells from tissues such as bone to contribute to the regeneration of other mesenchymal tissues such as the dermis. • Pdgfra -expressing mesenchymal cells from uninjured digits establish the blastema • Adult digit tip regeneration is distinct from embryonic digit development • The blastema state is environmentally determined • The regenerative environment enables mesenchymal lineage plasticity Storer et al. use lineage tracing, single-cell RNA sequencing, and cell transplantation to define the transcriptional identity of the mesenchymal cells comprising the blastema and the major transitions during mammalian digit tip regeneration. The regenerative environment determines the adult blastema state and confers mesenchymal lineage flexibility. [ABSTRACT FROM AUTHOR]