Finding HSCs in a Crowd Bone Marrow Cells

Early Attempts at Enriching Hematopoietic Stem Cells from Mixed Cell Populations

The acronym “LSK” stands for “Lineage^– Sca-1 ⁺ c-Kit⁺” and it was initially used to identify a population of cells enriched for hematopoietic stem cells (HSCs) in mice. The lineage-negative (Lin^–) fraction excludes differentiated blood cells, and the cells are further characterized by the presence of Sca-1 (Stem Cell Antigen-1) and c-Kit, which is also known as CD117. Sca-1 and c-Kit are cell surface markers associated with stem and progenitor cell populations.

The LSK phenotype was first employed as a way to isolate and study a population of cells enriched for HSCs in murine (mouse) bone marrow. The Lin⁻ gate excludes mature blood cells, and within this gate, the Sca-1⁺ c-Kit⁺ population was found to be enriched for hematopoietic stem and progenitor cells.

Further Efforts to Characterize True HSCs

Since the identification of LSK cells, researchers have continued to refine the characterization of hematopoietic stem cells using additional markers and functional assays. While LSK cells are enriched for HSCs, it’s important to note that not all LSK cells possess long-term repopulating capacity, which is a hallmark of true HSCs.

To further define and isolate HSCs, researchers have employed a combination of cell surface markers, such as CD150 (also known as Slamf1) and CD48, along with other functional assays. The CD150⁺ CD48⁻ LSK population, for example, has been shown to be highly enriched for long-term repopulating HSCs in mice. Other markers, such as CD34, have also been used to distinguish between HSCs and more committed progenitor cells.

Moreover, advances in single-cell technologies and lineage tracing techniques have provided researchers with more sophisticated tools to study the heterogeneity and lineage potential of individual hematopoietic cells. The field continues to evolve as researchers strive to better understand the molecular and functional characteristics of hematopoietic stem cells in both mice and humans.

Next Topic: The Initial Stages of Hematopoiesis

Source: ChatGPT response prompted and edited by Joel Graff.

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