Lymphoid-Biased Hematopoietic Stem Cells Are Maintained with Age and Efficiently Generate Lymphoid Progeny

Stem Cell Reports
Encarnacion Montecino-RodriguezPeter D Pioli

Abstract

Current models propose that reductions in the number of lymphoid-biased hematopoietic stem cells (Ly-HSCs) underlie age-related declines in lymphopoiesis. We show that Ly-HSCs do not decline in number with age. Old Ly-HSCs exhibit changes in gene expression and a myeloid-biased genetic profile, but we demonstrate that they retain normal lymphoid potential when removed from the old in vivo environment. Additional studies showing that interleukin-1 inhibits Ly-HSC lymphoid potential provide support for the hypothesis that increased production of inflammatory cytokines during aging underlies declines in lymphocyte production. These results indicate that current models proposing that lymphopoiesis declines with age due to loss of Ly-HSCs require revision and provide an additional perspective on why lymphocyte development in the elderly is attenuated.

Citations

Sep 10, 2019·Aging Cell·Gregory M FahySteve Horvath
Nov 20, 2019·Nature Reviews. Immunology·Kenneth DorshkindHans-Reimer Rodewald
Jul 18, 2020·Journal of Leukocyte Biology·Kylie M QuinnMagdalena Plebanski
Apr 19, 2020·Blood·Hanqing HeJianwei Wang
May 14, 2020·Current Opinion in Hematology·Georgina A AndersonKatie L Kathrein
Dec 12, 2019·Frontiers in Immunology·Peter D Pioli
Jun 26, 2020·Annual Review of Cell and Developmental Biology·Joseph N PucellaBoris Reizis
Oct 25, 2020·Nature Reviews. Immunology·Enrico VelardiMarcel R M van den Brink
Nov 25, 2020·Journal of Hematology & Oncology·Lei ZhangJiwang Zhang
Dec 31, 2020·STAR Protocols·Encarnacion Montecino-Rodriguez, Kenneth Dorshkind
Mar 3, 2021·Developmental Biology·Camila V Ramos, Vera C Martins
Jun 4, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Laura R Goldberg
Jun 3, 2021·Cancers·Meriem Ben KhoudCarine Brinster
Nov 13, 2021·Science Advances·Jette LengefeldAngelika Amon
Jan 16, 2022·Clinical Reviews in Allergy & Immunology·Augusto BleveAntonio Sica
Nov 6, 2020··Kenneth Dorshkind, Encarnacion Montecino-Rodriguez

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Methods Mentioned

BETA
Fluorescence-activated cell sorting
FACS
flow cytometry
PCR
RNA-seq

Software Mentioned

R
STAR
Metascape
MATLAB
DESeq2
SaVanT

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