Spatial mapping of human hematopoiesis at single-cell resolution reveals aging-associated topographic remodeling

Aleksandr Sarachakov, Arina Varlamova, Viktor Svekolkin, Margarita Polyakova, Itzel Valencia, Caitlin Unkenholz, Tania Pannellini, Ilia Galkin, Pavel Ovcharov, Dmitrii Tabakov, Ekaterina Postovalova, Nara Shin, Isha Sethi, Alexander Bagaev, Tomer Itkin, Genevieve Crane, Michael Kluk, Julia Geyer, Giorgio Inghirami, Sanjay Patel

Research output: Contribution to journalArticlepeer-review


The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized BM core biopsy tissue specimens, providing a rich resource for studying the intact human BM topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence–based digital whole slide image analysis and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging. Our data indicate heterogeneity in marrow adipose tissue (MAT) content within each age group and an inverse correlation between MAT content and proportions of early myeloid and erythroid precursors, irrespective of age. We identify consistent endosteal and perivascular positioning of hematopoietic stem and progenitor cells (HSPCs) with medullary localization of more differentiated elements and, importantly, uncover new evidence of aging-associated changes in cellular and vascular morphologies, microarchitectural alterations suggestive of foci with increased lymphocytes, and diminution of a potentially active megakaryocytic niche. Overall, our findings suggest that there is topographic remodeling of human hematopoiesis associated with aging. More generally, we demonstrate the potential to deeply unravel the spatial biology of normal and pathologic human BM states using intact archival tissue specimens.

Original languageEnglish
Pages (from-to)2282-2295
Number of pages14
Issue number26
StatePublished - 28 Dec 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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