Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed

Stonehouse, OJ; Biben, C; Weber, TS; Garnham, A; Fennell, KA; Farley, A; Terreaux, AF; Alexander, WS; Dawson, MA; Naik, SH; Taoudi, S

Author(s): Stonehouse, OJ; Biben, C; Weber, TS; Garnham, A; Fennell, KA; Farley, A; Terreaux, AF; Alexander, WS; Dawson, MA; Naik, SH; Taoudi, S;
Details: Publication Year 2024-07-24,Volume 19,Issue #8,Page 1189-1204
Journal Title: Stem Cell Reports
Abstract: It has been proposed that adult hematopoiesis is sustained by multipotent progenitors (MPPs) specified during embryogenesis. Adult-like hematopoietic stem cell (HSC) and MPP immunophenotypes are present in the fetus, but knowledge of their functional capacity is incomplete. We found that fetal MPP populations were functionally similar to adult cells, albeit with some differences in lymphoid output. Clonal assessment revealed that lineage biases arose from differences in patterns of single-/bi-lineage differentiation. Long-term (LT)- and short-term (ST)-HSC populations were distinguished from MPPs according to capacity for clonal multilineage differentiation. We discovered that a large cohort of long-term repopulating units (LT-RUs) resides within the ST-HSC population; a significant portion of these were labeled using Flt3-cre. This finding has two implications: (1) use of the CD150+ LT-HSC immunophenotype alone will significantly underestimate the size and diversity of the LT-RU pool and (2) LT-RUs in the ST-HSC population have the attributes required to persist into adulthood.
Publisher: Cell Press
Keywords: Animals; *Hematopoietic Stem Cells/cytology/metabolism; *Hematopoietic Stem Cell Transplantation; *Cell Lineage; Mice; Cell Differentiation; Fetus/cytology; Immunophenotyping; Hematopoiesis; Clone Cells/cytology
Research Division(s): Immunology; Epigenetics And Development; Immunology
PubMed ID: 39094562
Publisher's Version: https://doi.org/10.1016/j.stemcr.2024.07.003
Open Access at Publisher's Site: https://doi.org/10.1016/j.stemcr.2024.07.00
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-14 09:49:44

Last Modified: 2024-08-23 02:56:07