Related Experiment Video

Updated: Feb 13, 2026

Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells

Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells

Published on: November 1, 2017

Maternal Obesity Reprograms Differentiation Trajectories of Fetal Hematopoietic Stem and Progenitor Cells Through

Brianna M Doratt¹, Hami Hemati¹, Sheridan B Wagner¹

¹Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, United States.

Biorxiv : the Preprint Server for Biology

|February 12, 2026

Insights

Maternal obesity alters fetal immune cell development in the bone marrow, leading to reduced stem cells and an inflammatory bias in offspring. This impacts future immunity and disease risk.

Area of Science:

Immunology
Developmental Biology
Reproductive Health

Background:

Maternal obesity poses global health risks, particularly impacting offspring development.
The fetal immune system's development is poorly understood in the context of maternal obesity.
Disruptions in fetal bone marrow (FBM) hematopoiesis can lead to lifelong immune deficits.

Purpose of the Study:

To investigate how maternal obesity affects fetal bone marrow hematopoiesis in nonhuman primates.
To characterize changes in hematopoietic stem and progenitor cell (HSPC) populations and immune function.

Main Methods:

Utilized spectral flow cytometry and single-cell RNA sequencing to analyze FBM.
Employed functional differentiation assays to assess immune cell capabilities.
Mapped progenitor composition, lineage trajectories, and transcriptional programs.

Main Results:

Maternal obesity reduced CD34+ HSPCs and common lymphoid progenitors but increased megakaryocyte-erythroid and granulocyte-monocyte progenitors.
Observed altered progenitor maturation with accumulation at early differentiation stages.
Identified an inflammatory bias in myeloid progenitors and impaired monocyte function (migration, colony stimulation, exaggerated TNFα response).

Conclusions:

Maternal obesity disrupts FBM hematopoiesis, altering HSPC maturation and lineage trajectories.
Induces an inflammatory bias in the fetal immune system, even without an obesogenic diet.
These changes have potential long-term consequences for offspring immunity and health.

Read full analysis

Abstract

Background:

Maternal obesity is a global health challenge with profound consequences for offspring health. While its impact on metabolic programming has been widely studied, far less is known about how maternal obesity shapes the fetal immune system. The fetal bone marrow (FBM) is the central site of hematopoietic stem and progenitor cell (HSPC) development, and disruptions in this niche can have lifelong effects on immunity, infection susceptibility, and inflammatory disease risk. In this study, we examined FBM hematopoiesis in a nonhuman primate model of spontaneous maternal obesity.

Methods:

Using spectral flow cytometry, single cell RNA sequencing, and functional differentiation assays, we mapped progenitor composition, lineage trajectories, and immune function in offspring exposed to maternal obesity compared with lean controls. These complementary approaches allowed us to capture cellular frequencies and transcriptional programs, while trajectory and signaling analyses provided insight into how progenitor maturation and intercellular communication are disrupted by maternal obesity.

Results:

Our findings reveal that maternal obesity decreases CD34+ HSPCs and common lymphoid progenitor populations, while expanding megakaryocyte erythroid and granulocyte monocyte progenitors. Pseudotime analysis demonstrated altered maturation, with cells accumulating at early differentiation states. Transcriptional profiling uncovered a strong inflammatory bias, with myeloid progenitors upregulating alarmins, interferon stimulated genes, and proinflammatory mediators. Functionally, monocytes derived from obese FBM showed impaired migratory and colony stimulating capacity, coupled with exaggerated TNFα responses to LPS stimulation.

Conclusion:

Together, these results demonstrate that maternal obesity, even in the absence of obesogenic diet, disrupts fetal bone marrow hematopoiesis by altered HSPC maturation, reprogramming lineage trajectories, and inducing inflammatory bias.

Keywords:

bone marrow fetal development hematopoietic stem and progenitor cells lymphopoiesis maternal programming myelopoiesis nonhuman primates obesity

More Related Videos

Analysis of Hematopoietic Stem Progenitor Cell Metabolism

Analysis of Hematopoietic Stem Progenitor Cell Metabolism

Published on: November 9, 2019

Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells

Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells

Published on: February 15, 2019

Related Concept Videos

Multipotency of Hematopoietic Stem Cells

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...

Regulation of Hematopoietic Stem Cells

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...

Differentiation of Common Myeloid Progenitor Cells

Differentiation of Common Myeloid Progenitor Cells

Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...

Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...

Orthogonal Trajectories

Orthogonal Trajectories

Orthogonal trajectories describe the geometric relationship between two families of curves that intersect each other at right angles. One illustrative case involves a family of parabolas that open sideways along the x-axis. These curves share a common shape but differ by a scaling parameter, resulting in a set of curves that all pass through the origin and widen at different rates.Determining Orthogonal TrajectoriesTo identify the orthogonal trajectories for these parabolas, the first step...

Adult Stem Cells

Adult Stem Cells

Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...

Articles linked to this work by shared authors, journal, and citation graph.

Chronic alcohol consumption disrupts the gut microbial and metabolic landscapes.

Frontiers in microbiology·2026

Characterizing immune perturbations in peripheral blood following the East Palestine, Ohio train derailment.

Journal of exposure science & environmental epidemiology·2026

Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications to Promote Osteoclastogenesis.

Biology·2026

Spontaneous Pregravid Obesity Reshapes Fetal Immune Ontogeny in a Nonhuman Primate Model.

bioRxiv : the preprint server for biology·2026

Transcriptional signatures of rapid protection from Sudan virus infection by a single dose of a vesicular stomatitis virus-based vaccine.

PLoS pathogens·2026

Alcohol consumption exacerbates high-fat diet-mediated disruptions in myelopoiesis and osteoclastogenesis in mouse models of metabolic dysfunction-associated liver diseases.

Frontiers in endocrinology·2026

See all related articles