Objetivo
FateMapB aims to understand how the unique differentiation potential of fetal hematopoietic stem and progenitor cells
(HSPCs) contribute to functionally distinct cell types of the adult immune system. While most immune cells are replenished
by HSPCs through life, others emerge during a limited window in fetal life and sustain through self-renewal in situ. The
lineage identity of fetal HSPCs, and the extent of their contribution to the adult immune repertoire remain surprisingly
unclear. I previously identified the fetal specific RNA binding protein Lin28b as a post-transcriptional molecular switch
capable of inducing fetal-like hematopoiesis in adult bone marrow HSPCs (Yuan et al. Science, 2012). This discovery has
afforded me with unique perspectives on the formation of the mammalian immune system. The concept that the mature
immune system is a mosaic of fetal and adult derived cell types is addressed herein with an emphasis on the B cell lineage.
We will use two complementary lineage-tracing technologies to stratify the immune system as a function of developmental
time, generating fundamental insight into the division of labor between fetal and adult HSPCs that ultimately provides
effective host protection.
Aim 1. Determine the qualitative and quantitative contribution of fetal HSPCs to the mature immune repertoire in situ
through Cre recombination mediated lineage-tracing.
Aim 2. Resolve the disputed lineage relationship between fetal derived B1a cells and adult derived B2 cells by single cell
lineage-tracing using cellular barcoding in vivo.
Aim 3. Characterize the mechanism and effector functions of Lin28b induced B1a cell development for assessing the
clinical utility of inducible fetal-like lymphopoiesis.
The implications of FateMapB extend beyond normal development to immune regeneration and age-related features of
leukemogenesis. Finally, our combinatorial lineage-tracing approach enables dissection of cell fates with previously
unattainable resolution.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
22100 Lund
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