Biology subjects

Ysasi, A. B.

Publications and source records attributed to Ysasi, A. B..

3 recordsLinked to original sources

bioRxiv2025

High resolution spatial profiling of the hematopoietic landscape of the murine lung

Our current understanding of blood cell development and functionality stems primarily from the investigation of adult bone marrow (BM) and the fetal liver prenatally. However, emerging evidence highlights the lung as a previously underappreciated residence for hematopoietic cells. While a diversity of cells specific to the BM are known to promote the maturation and trafficking of hematopoietic cells, how the lung niche influences the development and functionality of resident cells is not known. Spatial in situ transcriptomics enables accurate mapping of cell identities and interactions within intact tissue, providing insights not accessible by dissociated single-cell profiling. Here, we present a high-resolution spatial transcriptomic atlas of the healthy adult murine lung placing specific emphasis on the hemato-endothelial landscape of this organ. As a case study, we developed a semi-automatic workflow to explicitly identify and curate rare - often multinucleated - megakaryocytes, requiring a combination of hex-binning spatial enrichment of canonical markers, expert curation, and cell boundary merging to correct for segmentation artifacts. We then characterized the spatial neighborhoods of megakaryocytes, illustrating their topological embedding within vascular, stromal, and immune microenvironments. Finally, we demonstrated the utility of this dataset for hypothesis-driven signaling studies by examining ligand-receptor interactions across pathways including BMP, VEGF, and ECM-integrin signaling. Together, this work defines the lung-blood niche and advances our understanding of the organ-specific properties of blood cells. We also provide a high-resolution spatial reference for the murine lung and demonstrate how targeted spatial in situ transcriptomics enable focused case studies of rare hematopoietic niches. KEY POINTSO_LIThis work represents the highest resolution gene expression mapping of the spatial symbiosis between the hematopoietic and pulmonary systems. C_LIO_LIPulmonary megakaryocytes localize within distinct vascular and stromal neighborhoods. C_LI

cell biology↗

bioRxiv2022

DE-NOVO HEMATOPOIESIS FROM THE FETAL LUNG

Hemogenic endothelial cells (HECs) are specialized cells that undergo endothelial to hematopoietic transition (EHT) to give rise to hematopoietic progenitors. Though not defined as a hematopoietic organ, the lung houses many resident hematopoietic cells, aids in platelet biogenesis, and is a reservoir for hematopoietic stem and progenitor cells (HSPCs), but lung HECs have never been described. Using explant cultures of murine and human fetal lungs, we demonstrate that the fetal lung is a source of HECs that have the functional capacity to undergo EHT to produce de-novo HSPCs. Flow cytometric and functional assessment of fetal lung explants showed the production of HSPCs that expressed key EHT and pre-HSPC markers. scRNA-Seq and small molecule modulation demonstrated that fetal lung EHT is reliant on canonical EHT signaling pathways. These findings suggest that functional HECs are present in the fetal lung, thus establishing this location as a potential extramedullary site of de-novo hematopoiesis.

developmental biology↗

bioRxiv2020

Airway-associated macrophages in homeostasis and repair

There is an increasing appreciation for the heterogeneity of myeloid lineages in the respiratory system, but whether distinct populations associate with the conducting airways remains unknown. We use single cell RNA sequencing, flow cytometry and immunofluorescence to characterize myeloid cells of the mouse trachea during homeostasis and epithelial injury/repair. We identify submucosal macrophages that are similar to lung interstitial macrophages and intraepithelial macrophages, and find that repair of the tracheal epithelium is impaired in Ccr2-deficient mice. Following injury there are early increases in neutrophils and submucosal macrophages, including M2-like macrophages. Unexpectedly, intraepithelial macrophages are initially lost but later replaced from CCR2+ monocytes. Mast cells and group 2 innate lymphoid cells are sources of IL13 that polarizes macrophages and directly influences basal cell behaviors. Their proximity to the airway epithelium establishes these myeloid populations as potential therapeutic targets for airway disease.

cell biology↗