Current Stem Cell Reports

, Volume 5, Issue 4, pp 133–144 | Cite as

Paradigms That Define Lung Epithelial Progenitor Cell Fate in Development and Regeneration

  • Aravind Sivakumar
  • David B. FrankEmail author
Prenatal Therapies (W Peranteau, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Prenatal Therapies


Purpose of Review

Throughout the lifespan, lung injury impedes the primary critical function essential for life-respiration. To repair quickly and efficiently is critical and is orchestrated by a diverse repertoire of progenitor cells and their niche. This review incorporates knowledge gained from early studies in lung epithelial morphogenesis and cell fate and explores its relevance to more recent findings of lung progenitor and stem cells in development and regeneration.

Recent Findings

Cell fate in the lung is organized into an early specification phase and progressive differentiation phase in lung development. The advent of single-cell analysis combined with lineage analysis and projections is uncovering new functional cell types in the lung, providing a topographical atlas for progenitor cell lineage commitment during development, homeostasis, and regeneration.


Lineage commitment of lung progenitor cells is spatiotemporally regulated during development. Single-cell sequencing technologies have significantly advanced our understanding of the similarities and differences between developmental and regenerative cell fate trajectories. Subsequent unraveling of the molecular mechanisms underlying these cell fate decisions will be essential to manipulating progenitor cells for regeneration.


Lung development Progenitor cells Cell fate Lung regeneration Differentiation 



Due to space limitations, we apologize to our scientific colleagues whose work could not be cited. We would like to thank Dr. Jarod Zepp for the critical review of this manuscript.

Funding Information

This work was supported by grants from the National Institutes of Health K08-HL140129 (D.B.F), the Parker B. Francis Foundation (D.B.F.), and the W.W. Smith Charitable Trust.

Compliance with Ethical Standards

Conflict of Interest

Aravind Sivakumar and David B. Frank declare that they have no conflict of interest

Human and Animal Rights and Informed Consent

This manuscript does not contain any original studies involving human or animal subjects.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Cardiology, Department of PediatricsChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Penn-CHOP Lung Biology InstituteUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Penn Cardiovascular InstituteUniversity of PennsylvaniaPhiladelphiaUSA

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