Preprint Article Version 1 This version is not peer-reviewed

Direct Interaction Between CD34+ Hematopoietic Stem Cells and Mesenchymal Stem Cells Reciprocally Preserves Stemness

Version 1 : Received: 29 September 2024 / Approved: 30 September 2024 / Online: 30 September 2024 (09:44:45 CEST)

How to cite: Safi, R.; Mohsen-Kanson, T.; Kouzi, F.; El-Saghir, J.; Dermesrobian, V.; Zugasti, I.; Zibara, K.; Menéndez, P.; El Hajj, H.; El-Sabban, M. Direct Interaction Between CD34+ Hematopoietic Stem Cells and Mesenchymal Stem Cells Reciprocally Preserves Stemness. Preprints 2024, 2024092390. https://doi.org/10.20944/preprints202409.2390.v1 Safi, R.; Mohsen-Kanson, T.; Kouzi, F.; El-Saghir, J.; Dermesrobian, V.; Zugasti, I.; Zibara, K.; Menéndez, P.; El Hajj, H.; El-Sabban, M. Direct Interaction Between CD34+ Hematopoietic Stem Cells and Mesenchymal Stem Cells Reciprocally Preserves Stemness. Preprints 2024, 2024092390. https://doi.org/10.20944/preprints202409.2390.v1

Abstract

A specialized microenvironment in the bone marrow, composed of stromal cells including mesenchymal stem cells (MSCs), support hematopoietic stem cells (HSCs) self-renewal and differentiation but also regulates leukemia development and progression. The reciprocal direct interaction between MSCs and CD34+ HSCs under physiological and pathological conditions has not been well characterized yet. Here, we established a direct co-culture model between MSCs and CD34+ HSCs or MSCs and acute myeloid leukemia cells (THP-1, Molm-13, and primary cells from patients) to study cell-cell communication. Following MSCs-CD34+ HSCs co-culture, the expression of adhesion markers N-cadherin and connexin 43 increased in both cell types, forming gap junction channels. Moreover, the clonogenic potential of CD34+ HSCs was increased. However, direct contact of acute myeloid leukemia cells with MSCs reduced the expression levels of connexin 43 and N-cadherin in MSCs. The impairment in gap junction formation could be ascertained to a defect in the acute myeloid leukemia derived MSCs. Interestingly, CD34+ HSCs and acute myeloid leukemia cell lines restrained MSCs from engaging into osteoblastic differentiation upon prolonged direct cell-cell contact. In conclusion, under physiological conditions, connexin 43 and N-cadherin interaction preserves stemness of both CD34+ HSCs and MSCs, a process that is compromised in acute myeloid leukemia, pointing out to the possible role of gap junctions in modulating stemness.

Keywords

Bone marrow, microenvironment; CD34+ hematopoietic stem cells; mesenchymal stem cells; connexin 43; N-cadherin; gap junction; acute myeloid leukemia; direct contact.

Subject

Biology and Life Sciences, Other

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