Orchestration of human multi-lineage hematopoietic cell development by humanized in vivo bone marrow models

被引：0

作者：

Renou, Laurent ^{[1
,2
,3
]}

Sun, Wenjie ^{[4
]}

Friedrich, Chloe ^{[5
]}

Galant, Klaudia ^{[1
,2
,3
]}

Conrad, Cecile ^{[4
]}

Consalus, Anne ^{[1
,2
,3
]}

Plantier, Evelia ^{[1
,2
,3
]}

Schallmoser, Katharina ^{[6
,7
]}

Krisch, Linda ^{[6
,7
]}

Barroca, Vilma ^{[1
,3
,8
]}

Devanand, Saryami ^{[1
,3
,8
]}

Dechamps, Nathalie ^{[1
,3
,9
]}

Reinisch, Andreas ^{[10
,11
]}

Martinovic, Jelena ^{[12
]}

Magnani, Alessandra ^{[13
]}

Faivre, Lionel ^{[14
]}

Lewandowski, Daniel ^{[1
,2
,3
]}

Calvo, Julien ^{[1
,2
,3
]}

Perie, Leila ^{[4
]}

Kosmider, Olivier ^{[2
,5
]}

Pflumio, Francoise ^{[1
,2
,3
]}

机构：

[1] Univ Paris Cite, CEA, Inserm, LSHL iRCM IBFJ,Stabil Genet Cellules Souches & Rad, Fontenay Aux Roses, France

[2] Org Partnerships Leukemia, OPALE Carnot Inst, Paris, France

[3] Univ Paris Saclay, CEA, Inserm, LSHL iRCM IBFJ,Stabil Genet Cellules Souches & Rad, Fontenay Aux Roses, France

[4] Sorbonne Univ, Univ PSL, CNRS, Lab Phys Chimie Curie,Inst Curie,UMR168, Paris, France

[5] Univ Paris Cite, Inst Cochin, CNRS, INSERM,U1016,UMR8104, Paris, France

[6] Paracelsus Med Univ, Dept Transfus Med, Salzburg, Austria

[7] Paracelsus Med Univ, GMP Unit, Salzburg, Austria

[8] CEA, IRCM, Anim Experimentat Platform, Fontenay Aux Roses, France

[9] CEA, IRCM, Flow Cytometry Platform, Fontenay Aux Roses, France

[10] Med Univ Graz, Dept Internal Med, Div Hematol, Graz, Austria

[11] Med Univ Graz, Dept Blood Grp Serol & Transfus Med, Graz, Austria

[12] Hop Antoine Beclere, AP HP, Fetal Pathol Unit, Clamart, France

[13] Hop Necker Enfants Malad, Biotherapy Dept, Paris, France

[14] St Louis Hosp, AP HP, Cell Therapy Unit, Paris, France

来源：

HEMASPHERE | 2025年 / 9卷 / 04期

关键词：

HUMAN CORD BLOOD; SINGLE-CELL; STEM-CELLS; MICE; NICHE; XENOTRANSPLANTATION; TRANSPLANTATION; ENGRAFTMENT; ENABLES;

D O I：

10.1002/hem3.70120

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate the differentiation and preservation of hematopoietic stem and progenitor cells (HSPCs). Immune-deficient murine models have enabled the analysis of molecular and cellular regulation of human HSPCs, but the physiology of these models is questioned as human hematopoietic cells develop in xenogenic microenvironments. In this study, we thoroughly characterized a humanized (h) in vivo BM model, developed from fetal (F/) and post-natal (P-N/) mesenchymal stromal cell (MSC) differentiation (called hOssicles [hOss]), in which human hematopoietic cells are generated following the transplantation of CD34+ cells. Serial isolation and transplant experiments of hMSCs and HSPCs from hOss revealed the dynamic nature of these hBM niches. hOss modified human hematopoietic development by modulating myeloid/lymphoid cell production and HSPC levels, with no major transcriptional changes in HSPCs at the single-cell level. Clonal tracking using genetic barcodes highlighted hematopoietic cell cross-talks between the endogenous murine BM and hOss and differences in clonal myeloid/multipotent cell production between F/hOss and P-N/hOss, uncovering ontogeny-related impact of the BM on human hematopoietic cell production.

引用

页数：17

共 39 条

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