Research Topic

Lineage Tracing, Hematopoietic Stem Cell and Immune Cell Dynamics

About this Research Topic

The immune system consists of a large repertoire of cellular components that are sustained by the concerted action of hematopoietic stem and progenitor cells throughout development and the lifetime of an organism. Recent experimental lineage tracing approaches, including those that utilize somatic mutations or viral integration sites as (natural) genetic barcodes, have opened up novel research avenues and enabled fundamental discoveries. Some of the most important relate to the characterization of cellular dynamics, ontology and differentiation paths of immune progenitor cells to their mature counterparts. This includes elucidating the developmental origin of innate-like lymphocytes or further resolving immune responses orchestrated by innate and adaptive lymphocytes. Moreover, the integration and the continuing innovation of single cell (multi)-omics approaches will further enhance researcher’s capabilities to facilitate biological discoveries in this area.

This Research Topic aims to highlight recent advances and discoveries in the area of stem cell dynamics and lineage tracing that have enabled new capabilities and insights into the shaping, maintenance and plasticity of the hematopoietic and immune systems. In particular, key features of competent immune responses may be revealed by charting dynamics during homeostasis and subsequently, their perturbations in disease. Additionally, we aim to discuss remaining fundamental or emerging biological challenges, e.g. technical limitations or how to bridge findings from model organisms to human immunology, as well as outline possible solutions and necessary innovations to further push scientific discoveries in this area.

We welcome all forms of submissions related to experimental/computational lineage and clonal tracing approaches as well as the different cellular compartments that make up the immune system. We would in particular encourage authors to critically discuss shortcomings of existing approaches and outline necessary innovations to further advance this area of research. Subjects of interest include, but are not limited to:

- Clonal and cellular dynamics in the innate and adaptive immune systems
- Immune cell dynamics and heterogeneity during infection and tumor evolution
- Hematopoietic stem cell heterogeneity
- Intra-individual longitudinal immune and stem cell dynamics (through sequential sampling)
- Developmental ontogeny of immune cells
- DNA barcoding strategies using viral vectors
- Genomic engineering approaches
- Use of viral integration sites in the context of gene therapy
- Use of “natural” genetics barcodes, such as T or B cell receptor sequences and somatic mutations, including in the nuclear and mitochondrial genome
- Sequencing approaches in this area
- Clonal immune cell dynamics in response to vaccines, viruses, and other pathogens, including SARS-CoV2


Dr. Leif Ludwig and Dr. Caleb Lareau are named on patent applications related to technologies to enable mitochondrial DNA genotyping in single cells. Dr. Chiara Romagnani declares no competing interests in relation to the topic theme.


Keywords: Lineage Tracing, Clonal Dynamics, Immunopoiesis, Hematopoiesis, Single Cell Genomics, Barcoding


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The immune system consists of a large repertoire of cellular components that are sustained by the concerted action of hematopoietic stem and progenitor cells throughout development and the lifetime of an organism. Recent experimental lineage tracing approaches, including those that utilize somatic mutations or viral integration sites as (natural) genetic barcodes, have opened up novel research avenues and enabled fundamental discoveries. Some of the most important relate to the characterization of cellular dynamics, ontology and differentiation paths of immune progenitor cells to their mature counterparts. This includes elucidating the developmental origin of innate-like lymphocytes or further resolving immune responses orchestrated by innate and adaptive lymphocytes. Moreover, the integration and the continuing innovation of single cell (multi)-omics approaches will further enhance researcher’s capabilities to facilitate biological discoveries in this area.

This Research Topic aims to highlight recent advances and discoveries in the area of stem cell dynamics and lineage tracing that have enabled new capabilities and insights into the shaping, maintenance and plasticity of the hematopoietic and immune systems. In particular, key features of competent immune responses may be revealed by charting dynamics during homeostasis and subsequently, their perturbations in disease. Additionally, we aim to discuss remaining fundamental or emerging biological challenges, e.g. technical limitations or how to bridge findings from model organisms to human immunology, as well as outline possible solutions and necessary innovations to further push scientific discoveries in this area.

We welcome all forms of submissions related to experimental/computational lineage and clonal tracing approaches as well as the different cellular compartments that make up the immune system. We would in particular encourage authors to critically discuss shortcomings of existing approaches and outline necessary innovations to further advance this area of research. Subjects of interest include, but are not limited to:

- Clonal and cellular dynamics in the innate and adaptive immune systems
- Immune cell dynamics and heterogeneity during infection and tumor evolution
- Hematopoietic stem cell heterogeneity
- Intra-individual longitudinal immune and stem cell dynamics (through sequential sampling)
- Developmental ontogeny of immune cells
- DNA barcoding strategies using viral vectors
- Genomic engineering approaches
- Use of viral integration sites in the context of gene therapy
- Use of “natural” genetics barcodes, such as T or B cell receptor sequences and somatic mutations, including in the nuclear and mitochondrial genome
- Sequencing approaches in this area
- Clonal immune cell dynamics in response to vaccines, viruses, and other pathogens, including SARS-CoV2


Dr. Leif Ludwig and Dr. Caleb Lareau are named on patent applications related to technologies to enable mitochondrial DNA genotyping in single cells. Dr. Chiara Romagnani declares no competing interests in relation to the topic theme.


Keywords: Lineage Tracing, Clonal Dynamics, Immunopoiesis, Hematopoiesis, Single Cell Genomics, Barcoding


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

29 October 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

29 October 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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