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Emma Rawlins

rawlinsEmma Rawlins PhD, MRC Research Fellow, Member of the Department of Pathology.

Europe PMC | Pubmed

 

 

 

Stem and progenitor cells in the mammalian lung

rawlins 2013Our lungs have a complex three-dimensional structure which facilitates respiration and host defence. Building this structure requires that lung embryonic progenitor cells produce the correct types and numbers of cells in the correct sequence. How is this controlled? And how is the final structure maintained in the adult? Our lab investigates the cellular and molecular mechanisms which control stem and progenitor cell fate decisions in the developing and adult lungs. Key unanswered questions include what mechanisms control the decision of lung progenitors to self-renew or to differentiate? Which pathways are required for cell lineage specification in the lung? Our approach is to use the power of mouse genetics to understand the control of lung progenitor cell behaviour at the single cell level.This allows individual cells to be analysed quantitatively in vivo, or by live-imaging in organ culture systems.

We have previously shown that in the embryonic lung there is a population of Id2+ multipotent epithelial progenitor cells located at the distal tips of the budding epithelium.The developmental potential, or competence, of these cells changes during embryogenesis.At the same time the cells undergo a change in gene expression pattern.We are currently exploring the cellular and molecular basis of this change in competence.

The identity of the epithelial stem and progenitor cells in the postnatal lung remains controversial. Our previous work has shown that each anatomical region (trachea, bronchioles, alveoli) has its own progenitor cell population and that the behaviour of these progenitors can change in response to local conditions. Our current postnatal work focuses on:

• Better characterising the adult lung progenitor cells. This includes testing whether progenitor cell behaviour is widespread or there are stem cells. • Understanding the genetic regulation of the progenitors under several different physiologically-relevant conditions. In particular, we are focusing on genes that are hypothesised to control the decision to self-renew or differentiate.

Our long-term vision is to combine the developmental and homeostatic aspects of our work to develop new approaches to ameliorate human pulmonary disease. In particular, we are working towards being able specifically to direct endogenous lung stem cells to generate any lung epithelial cell type.

 

Selected publications:

• Rawlins EL, Okubo T, Xue Y, Brass DM, Auten RL, Hasegawa H,Wang F and Hogan BLM (2009)The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4 525-534

• Rawlins EL, Clark CP, Xue Y and Hogan BLM (2009) The Id2 distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development136 3741-3745

• Rawlins EL (2011) The building blocks of mammalian lung development. Developmental Dynamics 240 463-76

• Onaitis M, D’Amico TA, Clark C, Guinney J, Harpole DH and Rawlins EL ( 2011) A 10-gene progenitor cell signature predicts prognosis in lung adenocarcinoma. Annals of Thoracic Surgery 91 1046-50

 

groupRawlins2013

Plain English

Our ability to breathe at birth requires that during embryonic development our lungs make many types of specialized cells, arranged in a specific structure. This structure must then be maintained throughout life, even when the air that we breathe is contaminated by pollutants and toxins. Building and maintaining the lung involves progenitor cells. These cells divide to generate the different specialized cell types. Their divisions must be tightly controlled to ensure that our lungs always have the correct numbers and types of specialized cells. Misregulation of progenitor cell division results in changes to the lung structure which can contribute to important lung diseases, including asthma, emphysema and COPD (Chronic Obstructive Pulmonary Disease). Our work uses the power of mouse genetics to understand the control of lung progenitor cell division in both growing and adult lungs. This fundamental research is essential for understanding the changes that can occur in our lungs as they become diseased, and for the development of cell-based therapies for lung repair.

Co-workers

Gayan Balasooriya • Christoph Budjan • Mac Hughes • Jo-Anne Johnson • Usua Laresgoiti Garay • Marko Nikolic • Chandrika Rao