Hematopoiesis is the continuous, regulated physiological process of producing, replacing, and differentiating all blood cellular components, including red blood cells, white blood cells, and platelets from pluripotent hematopoietic stem cells (HSCs).
Primarily occurring in the bone marrow in adults, this process ensures a constant supply of blood and immune cells throughout life.
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How and when HSCs and/or their daughter cells decide to acquire a specific fate remains poorly understood.
Types of fate determinants
INTRINSIC
The fate of HSCs is controlled in part by internal programs within the cells themselves.
Key proteins called transcription factors act like switches, turning genes on or off to maintain healthy HSCs and direct their differentiation into specific blood and immune lineages, including T cells.
In addition, basic processes within the cell, such as how it produces energy, manages its genetic material, and controls growth and division, also play an important role.
EXTRINSIC
HSCs do not act alone - they are supported and regulated by their microenvironment, known as the “niche.”
These specialized areas, found in the bone marrow and other hematopoietic-supporting tissues, provide signals that help HSCs and progenitors survive, stay balanced, and produce the right types of blood cells.
Different nearby cells release factors and create conditions that guide how stem cells behave and develop.
CELL DIVISION PATTERNING
HSCs must balance making more of themselves with producing specialized blood cells. One way they do this is through how they divide.
During some divisions, key molecules are distributed unevenly between the two new cells, helping determine whether each cell remains a stem cell or begins to specialize.
This process helps maintain a healthy supply of HSCs while ensuring ongoing blood and immune cell production.
Origin of blood and immune cells
Fate of HSCs and downstream progenitors is governed by a complex interplay of intrinsic molecular programs, extrinsic signals from the bone marrow microenvironment, and the mechanics of cell division.
Furthermore, accumulating evidence indicates that diverse signals from the microenvironment actively support hematopoietic stem and progenitor cells (HSPCs), regulating their maintenance, activation, and lineage output.
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Despite these advances, the mechanisms by which niche-derived cues integrate with intrinsic programs to control HSPC fate decisions remain incompletely defined.​
OUR RESEARCH PROGRAM
Using bulk and single cell multi-omic approaches (including transcriptomic, genomic, and proteomic profiling), combined with in vivo tools that enable the study of HSPCs across developmental stages, our research aims to define how intrinsic programs and microenvironmental signals coordinate normal blood and immune cell development, with a particular focus on T-cell lineage specification.
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We have established an integrated experimental pipeline incorporating cell-marking strategies and relevant in vivo models to enable functional interrogation of HSPCs properties and hematopoietic fate regulation.
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This integrated program will generate new insight into the molecular mechanisms driving immune T-cell development and provide broadly applicable strategies for dissecting regulatory networks in hematopoiesis.​​
