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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368694 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2024.07.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Effect of Tumor Suppressor Gene Heterozygous Deletion on Hematopoietic System in Mice].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
October 2024
Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Objective: To explore the effect of heterozygous deletion of histone methyltransferase gene on the hematological system of mice.
Methods: CRISPR/Cas9 technology was used to construct mice model of heterozygous deletion () and the changes of whole blood cell count in mice were continuously monitored by blood routine test. The clonal expansion ability of bone marrow cells was explored by colony formation assay and the proportion of primitive hematopoietic cells, including long-term hematopoietic stem cell (LT-HSC), short-term hematopoietic stem cell (ST-HSC), and multipotent progenitor cell in mutant mice was analyzed by flow cytometry.
Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed.
Stem Cell Reports
August 2024
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; The University of Melbourne, Melbourne, Victoria, Australia; School of Cellular and Molecular Medicine, University of Bristol, Bristol, England, UK. Electronic address:
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.
View Article and Find Full Text PDFMicroenvironmental CXCL12 deletion enhances Flt3-ITD acute myeloid leukemia stem cell response to therapy by reducing p38 MAPK signaling.
Leukemia
March 2023
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Fms-like tyrosine kinase 3 (Flt3) tyrosine kinase inhibitors (Flt3-TKI) have improved outcomes for patients with Flt3-mutated acute myeloid leukemia (AML) but are limited by resistance and relapse, indicating persistence of leukemia stem cells (LSC). Here utilizing a Flt3-internal tandem duplication (Flt3-ITD) and Tet2-deleted AML genetic mouse model we determined that FLT3-ITD AML LSC were enriched within the primitive ST-HSC population. FLT3-ITD LSC showed increased expression of the CXCL12 receptor CXCR4.
View Article and Find Full Text PDFExogenous hydrogen sulfide and miR-21 antagonism attenuates macrophage-mediated inflammation in ischemia reperfusion injury of the aged kidney.
Geroscience
June 2021
Department of Physiology, University of Louisville School of Medicine, 500 S Preston St. HSC-A, Room 1115, Louisville, KY, 40202, USA.
Ischemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in the aging population. A reduction of hydrogen sulfide (HS) production in the old kidney and renal IRI contribute to renal pathology and injury. Recent studies suggest that microRNAs (miRs) play an important role in the pathophysiology of AKI and a significant crosstalk exists between HS and miRs.
View Article and Find Full Text PDFHoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic stem cell compartment.
Biochem Biophys Res Commun
February 2021
RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, Japan. Electronic address:
Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field have allowed us to analyze HSCs with single cell resolution and implicate that functional heterogeneity may exist even within the highly purified HSC compartment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!