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Blood and immune development in human fetal bone marrow and Down syndrome

Laura Jardine1,2, Simone Webb1, Issac Goh1

  • 1Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.

Nature
|September 30, 2021
PubMed

Insights

Fetal bone marrow (BM) rapidly develops a full range of blood and immune cells early in the second trimester. This study reveals fetal BM development and its alterations in Down syndrome.

Area of Science:

  • Developmental biology
  • Hematology
  • Immunology

Background:

  • Hematopoiesis in bone marrow (BM) is crucial for blood and immune cell production.
  • The development of fetal bone marrow (FBM) and its role in fetal and neonatal health remain largely unknown.
  • Understanding FBM development is key to comprehending early human hematopoiesis.

Purpose of the Study:

  • To investigate the developmental trajectory of fetal bone marrow (FBM), including its stromal components.
  • To characterize the multi-omic landscape of FBM during early human development.
  • To identify differences between FBM, fetal liver, and cord blood hematopoietic progenitors.

Main Methods:

  • Multi-omic assessment of mRNA and multiplexed protein epitope expression in FBM.
  • Comparative analysis of hematopoietic progenitors from fetal liver, FBM, and cord blood.
  • Investigation of vascular structures and microenvironment within FBM.

Main Results:

  • The complete blood and immune cell repertoire is established in FBM within a 6-7 week window in the second trimester.
  • FBM supports extensive myeloid cell diversification, including novel granulocyte, eosinophil, and dendritic cell subsets.
  • Significant expansion of B lymphocytes in FBM compared to fetal liver; distinct vascular compartmentalization observed.
  • Hematopoietic progenitors show tissue-specific transcriptional and functional differences.
  • Down syndrome (trisomy 21) is associated with disrupted B lymphocyte, erythroid, and myeloid development due to intrinsic and extrinsic factors.

Conclusions:

  • Fetal bone marrow (FBM) undergoes rapid and comprehensive development early in gestation, establishing the full spectrum of blood and immune cells.
  • Distinct cellular and microenvironmental characteristics of FBM contribute to fetal and neonatal hematopoiesis.
  • Alterations in FBM development and microenvironment are implicated in the hematological abnormalities observed in Down syndrome (trisomy 21).

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