TY - JOUR
T1 - B1 lymphocytes develop independently of Notch signaling during mouse embryonic development
AU - Portilho, Nathalia Azevedo
AU - Scarfo, Rebecca
AU - Bertesago, Elisa
AU - Ismailoglu, Ismail
AU - Kyba, Michael
AU - Kobayashi, Michihiro
AU - Ditadi, Andrea
AU - Yoshimoto, Momoko
N1 - Publisher Copyright:
© 2021 Company of Biologists Ltd. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - B1 lymphocytes are a small but unique component of the innate immune-like cells. However, their ontogenic origin is still a matter of debate. Although it is widely accepted that B1 cells originate early in fetal life, whether or not they arise from hematopoietic stem cells (HSCs) is still unclear. In order to shed light on the B1 cell origin, we set out to determine whether their lineage specification is dependent on Notch signaling, which is essential for the HSC generation and, therefore, all derivatives lineages. Using mouse embryonic stem cells (mESCs) to recapitulate murine embryonic development, we have studied the requirement for Notch signaling during the earliest B-cell lymphopoiesis and found that Rbpj-deficient mESCs are able to generate B1 cells. Their Notch independence was confirmed in ex vivo experiments using Rbpj-deficient embryos. In addition, we found that upregulation of Notch signaling induced the emergence of B2 lymphoid cells. Taken together, these findings indicate that control of Notch signaling dose is crucial for different B-cell lineage specification from endothelial cells and provides pivotal information for their in vitro generation from PSCs for therapeutic applications.
AB - B1 lymphocytes are a small but unique component of the innate immune-like cells. However, their ontogenic origin is still a matter of debate. Although it is widely accepted that B1 cells originate early in fetal life, whether or not they arise from hematopoietic stem cells (HSCs) is still unclear. In order to shed light on the B1 cell origin, we set out to determine whether their lineage specification is dependent on Notch signaling, which is essential for the HSC generation and, therefore, all derivatives lineages. Using mouse embryonic stem cells (mESCs) to recapitulate murine embryonic development, we have studied the requirement for Notch signaling during the earliest B-cell lymphopoiesis and found that Rbpj-deficient mESCs are able to generate B1 cells. Their Notch independence was confirmed in ex vivo experiments using Rbpj-deficient embryos. In addition, we found that upregulation of Notch signaling induced the emergence of B2 lymphoid cells. Taken together, these findings indicate that control of Notch signaling dose is crucial for different B-cell lineage specification from endothelial cells and provides pivotal information for their in vitro generation from PSCs for therapeutic applications.
KW - B1 cells
KW - B2 cells
KW - Hematopoietic stem cells
KW - Lymphopoiesis
KW - Mouse embryonic development
KW - Mouse embryonic stem cells
KW - Notch signaling
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UR - http://www.scopus.com/inward/citedby.url?scp=85113290989&partnerID=8YFLogxK
U2 - 10.1242/DEV.199373
DO - 10.1242/DEV.199373
M3 - Article
C2 - 34284495
AN - SCOPUS:85113290989
SN - 0950-1991
VL - 148
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 15
M1 - dev199373
ER -