Human lung development: recent progress and new challenges.

Marko Z Nikolić,Emma L Rawlins,Dawei Sun

doi:10.1242/dev.163485

Marko Z Nikolić, Emma L Rawlins + Show 1 more

Open Access

https://doi.org/10.1242/dev.163485

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Abstract

ABSTRACTRecent studies have revealed biologically significant differences between human and mouse lung development, and have reported new in vitro systems that allow experimental manipulation of human lung models. At the same time, emerging clinical data suggest that the origins of some adult lung diseases are found in embryonic development and childhood. The convergence of these research themes has fuelled a resurgence of interest in human lung developmental biology. In this Review, we discuss our current understanding of human lung development, which has been profoundly influenced by studies in mice and, more recently, by experiments using in vitro human lung developmental models and RNA sequencing of human foetal lung tissue. Together, these approaches are helping to shed light on the mechanisms underlying human lung development and disease, and may help pave the way for new therapies.

Highlights

Lung cancer is the most common cancer worldwide, and end-stage respiratory failure accounts for the third highest cause of mortality due to non-infectious disease (Global status report on noncommunicable diseases 2010, World Health Organization; http:// www.who.int/nmh/publications/ncd_report2010/en/)
The mortality is partly due to irreversible destruction of lung tissue and the inability to meet the demands for transplantation
Only recently have equivalent studies been performed using human embryonic lung tissue to allow induced pluripotent stem cells (iPSCs) differentiation attempts to be further improved and adequately validated (Miller et al, 2017; Nikolić et al, 2017). In this Review, we summarise our current knowledge of human lung development, highlighting areas of similarity to and divergence from mouse biology

Summary

Introduction

Lung cancer is the most common cancer worldwide, and end-stage respiratory failure accounts for the third highest cause of mortality due to non-infectious disease (Global status report on noncommunicable diseases 2010, World Health Organization; http:// www.who.int/nmh/publications/ncd_report2010/en/). Human adult lung cell types The various cell types found in human lungs can be categorised into epithelium, endothelium (vasculature and lymphatics), pleura/ mesothelium, airway and vascular smooth muscle, pericytes, fibroblasts, neurons and immune cells such as alveolar macrophages Many of these cell types can be further classified based on their position along the epithelial branching tree. The pseudoglandular phase occurs from approximately 5 to 17 pcw (Fig. 2C,D) During this period, the lung continues to grow by branching morphogenesis, the airway tree is laid down and begins to differentiate with cartilage, and the smooth muscle and mucous glands are already visible. One experimental approach has been to grow late-stage (∼20 pcw) distal human lung epithelium in 2D as a model for AT2 and AT1 cell differentiation Such studies have led to important molecular insights, for example elucidating the roles of glucocorticoid signalling (Mendelson et al, 1997; Mishra et al, 2018). The culture of human foetal lung explants has allowed the effects of specific signalling activators and inhibitors on cell fate, proliferation

C Factors required for self-renewal

E Co-culture with matrix-embedded fibroblasts

Findings

Conclusions and future directions