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Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow.
Stem Cell Reports. 2020 Jun 26 [Online ahead of print]SC

Abstract

Age-related clonal hematopoiesis is a major risk factor for myeloid malignancy and myeloid skewing is a hallmark of aging. However, while it is known that non-cell-autonomous components of the microenvironment can also influence this risk, there have been few studies of how the spatial architecture of human bone marrow (BM) changes with aging. Here, we show that BM adiposity increases with age, which correlates with increased density of maturing myeloid cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) and an increased proportion of HSPCs adjacent to adipocytes. However, NGFR+ bone marrow stromal cell (NGFR+ BMSC) density and distance to HSPCs and vessels remained stable. Interestingly, we found that, upon aging, maturing myeloid cell density increases in hematopoietic areas surrounding adipocytes. We propose that increased adjacency to adipocytes in the BM microenvironment may influence myeloid skewing of aging HSPCs, contributing to age-related risk of myeloid malignancies.

Authors+Show Affiliations

Unidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.Unidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.Departamento de Patología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.Fluidigm Canada Inc., Markham, ON, Canada.Fluidigm Canada Inc., Markham, ON, Canada.Division of Hematopathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.División de Ortopedia, Hospital de Traumatología y Ortopedia Lomas Verdes, Instituto Mexicano del Seguro Social, Mexico City, Mexico.Unidad de Reemplazo Articular, Hospital de Traumatología y Ortopedia Lomas Verdes, Instituto Mexicano del Seguro Social, Mexico City, Mexico.Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: jdick@uhnresearch.ca.Unidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Electronic address: eugenia.flores-figueroa@uhnresearch.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32649902

Citation

Aguilar-Navarro, Alicia G., et al. "Human Aging Alters the Spatial Organization Between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow." Stem Cell Reports, 2020.
Aguilar-Navarro AG, Meza-León B, Gratzinger D, et al. Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow. Stem Cell Reports. 2020.
Aguilar-Navarro, A. G., Meza-León, B., Gratzinger, D., Juárez-Aguilar, F. G., Chang, Q., Ornatsky, O., Tsui, H., Esquivel-Gómez, R., Hernández-Ramírez, A., Xie, S. Z., Dick, J. E., & Flores-Figueroa, E. (2020). Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2020.06.011
Aguilar-Navarro AG, et al. Human Aging Alters the Spatial Organization Between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow. Stem Cell Reports. 2020 Jun 26; PubMed PMID: 32649902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow. AU - Aguilar-Navarro,Alicia G, AU - Meza-León,Berenice, AU - Gratzinger,Dita, AU - Juárez-Aguilar,Fany G, AU - Chang,Qing, AU - Ornatsky,Olga, AU - Tsui,Hubert, AU - Esquivel-Gómez,Ricardo, AU - Hernández-Ramírez,Antonio, AU - Xie,Stephanie Z, AU - Dick,John E, AU - Flores-Figueroa,Eugenia, Y1 - 2020/06/26/ PY - 2020/02/29/received PY - 2020/06/09/revised PY - 2020/06/10/accepted PY - 2020/7/11/entrez PY - 2020/7/11/pubmed PY - 2020/7/11/medline KW - BMSCs KW - CD34+ KW - adipocytes KW - aging KW - microenvironment KW - myeloid KW - niche KW - spatial KW - stem cells KW - stroma JF - Stem cell reports JO - Stem Cell Reports N2 - Age-related clonal hematopoiesis is a major risk factor for myeloid malignancy and myeloid skewing is a hallmark of aging. However, while it is known that non-cell-autonomous components of the microenvironment can also influence this risk, there have been few studies of how the spatial architecture of human bone marrow (BM) changes with aging. Here, we show that BM adiposity increases with age, which correlates with increased density of maturing myeloid cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) and an increased proportion of HSPCs adjacent to adipocytes. However, NGFR+ bone marrow stromal cell (NGFR+ BMSC) density and distance to HSPCs and vessels remained stable. Interestingly, we found that, upon aging, maturing myeloid cell density increases in hematopoietic areas surrounding adipocytes. We propose that increased adjacency to adipocytes in the BM microenvironment may influence myeloid skewing of aging HSPCs, contributing to age-related risk of myeloid malignancies. SN - 2213-6711 UR - https://www.unboundmedicine.com/medline/citation/32649902/Human_Aging_Alters_the_Spatial_Organization_between_CD34+_Hematopoietic_Cells_and_Adipocytes_in_Bone_Marrow L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-6711(20)30232-0 DB - PRIME DP - Unbound Medicine ER -
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