Murine Foetal Liver Supports Limited Detectable Expansion of Life-long Haematopoietic Progenitors

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2022 Oct 6

PMID 36202972

Authors

Miguel Ganuza

Trent Hall

Jacquelyn Myers

Chris Nevitt

Raul Sanchez-Lanzas

Ashley Chabot

Juan Ding

Emilia Kooienga

Claire Caprio

David Finkelstein

Guolian Kang

Esther Obeng

Shannon McKinney-Freeman

Affiliations

Soon will be listed here.

Abstract

Current dogma asserts that the foetal liver (FL) is an expansion niche for recently specified haematopoietic stem cells (HSCs) during ontogeny. Indeed, between embryonic day of development (E)12.5 and E14.5, the number of transplantable HSCs in the murine FL expands from 50 to about 1,000. Here we used a non-invasive, multi-colour lineage tracing strategy to interrogate the embryonic expansion of murine haematopoietic progenitors destined to contribute to the adult HSC pool. Our data show that this pool of fated progenitors expands only two-fold during FL ontogeny. Although Histone2B-GFP retention in vivo experiments confirmed substantial proliferation of phenotypic FL-HSC between E12.5 and E14.5, paired-daughter cell assays revealed that many mid-gestation phenotypic FL-HSCs are biased to differentiate, rather than self-renew, relative to phenotypic neonatal and adult bone marrow HSCs. In total, these data support a model in which the FL-HSC pool fated to contribute to adult blood expands only modestly during ontogeny.

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