Secretome-to-transcriptome linkage of bone marrow niche cells at single-cell resolution

Abstract

The functional decline of hematopoietic stem cells (HSCs) with age is a well-documented phenomenon, associated with various health complications, including anemia, impaired immune responses, and chronic inflammation. This dysfunction can contribute to the onset of hematological disorders such as myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) (Weeks et al., 2022).
HSCs depend on signals provided by bone marrow (BM) niche cells for their proper maintenance and function. These niche cells are also subject to age-related changes, including the loss of osteoblasts and lineage skewing towards adipocytes (Švajger et al., 2025).
Step 1 objective of this project is to establish a recently developed protocol at the Lund Stem Cell Center to investigate age-associated changes in BM niche cells. This work is based on prior research from our laboratory and our collaborators at Sanquin Lab, which identified the CD51:CD61 axis in HSCs and the availability of corresponding ligands in the niche environment as a conserved feature of aging in the mouse model. The full objective of the project was to identify the niche cells producing these ligands, characterize their expression profiles, and compare gene expression between young and aged mouse samples.
Although the project could not be fully completed due to an extended optimization phase and time constraints, we successfully applied an integrated single-cell approach, combining Nanovial-based secretion capture with single-cell RNA sequencing using the 10x Genomics Chromium platform. The implementation of this protocol opens the door to a deeper understanding of age-associated variations in niche cell populations and alterations in their secretory profiles. Ultimately, this approach will contribute to identifying key factors and cellular sources that support HSC function during aging.

Popular Abstract

What is causing our blood cell production center to be less efficient as we age?
Hematopoietic stem cells (HSCs) are essential for producing all types of blood cells - red blood cells, white blood cells, and platelets. These stem cells first develop in the embryo before migrating to the bone marrow, where they sustain blood production throughout adulthood. HSCs remain mostly in a resting state in the bone marrow, which helps protect them from damage. However, when the body needs more blood cells—such as during illness—HSCs become activated and begin producing differentiated blood cells. As we age, HSCs gradually become less efficient, paving the way for various health problems, such as cardiovascular diseases and blood cancers.
HSCs don’t function alone in the bone marrow; they depend on an environment known as the bone marrow niche, which acts as their support system. This niche is made up of various cell types that provide the necessary signals for HSC survival, multiplication, and differentiation. The niche is a complex and heterogeneous environment that we still don’t fully understand. As the body ages, the bone marrow environment undergoes changes, and these alterations can negatively affect the ability of HSCs to produce healthy blood cells.
To better understand these changes, we need advanced experimental techniques. My thesis work enabled the first implementation of a novel technique at Lund, combining single-cell RNA sequencing with Nanovials, which allowed us to analyze both gene activity and protein secretion in individual mouse cells. Single-cell RNA sequencing enables us to examine the specific gene activity in each cell, while Nanovials capture the proteins secreted by these cells, providing insight into which cells are producing the most important molecules for HSC function. By combining these tools, we can gain a deeper understanding of how aging affects individual cells and how gene expression and secretion are connected. Ultimately, this research may pave the way for new treatments for age-related blood disorders in humans.

• author: Boutard, Juliette Gabrielle Florence
• supervisor: Maria Jassinskaja
• organization: Department of Immunotechnology; Educational programmes, LTH
• course: KIMM01 20252
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• keywords: Hematopoietic Stem Cells, Bone Marrow Niche Cells, HSC-Niche Interaction, Age-related Blood Disorders, Secretome, Single-Cell RNA Sequencing, Nanovials, Lund Stem Cell Center
• language: English
• id: 9223430
• date added to LUP: 2026-03-03 20:53:56
• date last changed: 2026-03-03 20:53:56