# Understanding the Symbiosis Between Megakaryocytes and the Lung Microenvironment

> **NIH NIH F30** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $50,520

## Abstract

Abstract
Megakaryocytes (MKs) and the platelets they produce are essential for clot formation, but both are also
involved in critical processes such as development, inflammation, homeostasis and regeneration. Platelet
biogenesis is canonically thought to occur primarily in the adult bone marrow and the developing fetal liver. As
such, our current understanding of MK development stems primarily from the investigation of these tissues.
However, emerging evidence highlights the lung as a previously underappreciated residence for MKs, with
several groups demonstrating that lung-MKs significantly contribute to circulating platelet mass. While a
diversity of cells specific to the bone marrow are known to promote the maturation and trafficking of MKs,
investigation into how cells of the lung niche influence the development and function of MKs has not been
done. This knowledge gap is highlighted by the fact that platelets have demonstrated lung-specific roles in
processes such as development, epithelial protection against bacterial exotoxins, and pulmonary fibrosis.
Whether lung-MKs are involved in these processes and/or provide a localized source of platelets that carry out
lung-specific functions is unknown. This question led us to hypothesize that symbiotic interactions between
lung-MKs and the lung microenvironment aid in the maturation and functionalization of both MKs and the lung
itself. Here we propose the use of both in-vivo and in-vitro approaches to investigate this adaptive symbiosis.
In Aim 1, we will perform single cell RNA sequencing and functional assays on MKs isolated from fetal and
adult mouse tissues to define a lung-specific MK phenotype. Investigating MKs at different stages of
development will bolster our understanding of the maturational trajectory and functionalization of lung-MKs. We
will also perform the histological assessment of primary mouse lung tissue to determine the cellular makeup of
the lung-MK microenvironment. In Aim 2, we will develop an in-vitro human induced pluripotent stem cell
(iPSC) based coculture system to model the interaction of MKs in the lung microenvironment. Previous work
from the Murphy (Sponsor) and Kotton (Co-Sponsor) labs have established methodologies for directing the
patterning of iPSCs towards hematopoietic and lung lineages to robustly produce iPSC derived MKs and lung
organoids. Harnessing these tools, we will coculture MKs with lung organoids to investigate how reciprocal
interactions between each system influences the development and patterning of these tissues. Resultant cells
from coculture will then be subjected to functional and transcriptomic studies to investigate how the phenotypic
patterning of MKs and lung organoids is influenced by coculture. These studies will improve our understanding
of the biology of MK specification and platelet production, and also shed light on the symbiotic relationship
between the lung and resident MKs, thus introducing the previously undescribed role of ...

## Key facts

- **NIH application ID:** 10068337
- **Project number:** 1F30HL154552-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Anthony K Yeung
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068337

## Citation

> US National Institutes of Health, RePORTER application 10068337, Understanding the Symbiosis Between Megakaryocytes and the Lung Microenvironment (1F30HL154552-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10068337. Licensed CC0.

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